Dihalopropene compounds, insecticidal/acaricidal agents containing same, and intermediates for their production

ABSTRACT

The dihalopropene compounds of the general formula (I) have excellent insecticidal/acaricidal activity, so that they are satisfactorily effective for the control of noxious insects, mites and ticks.

TECHNICAL FIELD

[0001] The present invention relates to dihalopropene compounds,insecticidal/acaricidal agents containing these compounds as activeingredients, and intermediates for their production.

[0002] 1. Background Art

[0003] As disclosed in JP-A 48-86835/1973 and JP-A 49-1526/1974, forexample, it is well known that some kinds of propene compounds can beused as an active ingredient of insecticides.

[0004] In view of their insecticidal-acaricidal activity, it cannotalways be said that these compounds are satisfactorily effective for thecontrol of noxious insects, mites and ticks.

[0005] 2. Disclosure of Invention

[0006] The present inventors have intensively studied to find a compoundhaving excellent insecticidal/acaricidal activity. As a result, theyhave found that particular dihalopropene compounds have satisfactoryinsecticidal-acaricidal activity for the control of noxious insects,mites and ticks, thereby completing the present invention.

[0007] That is, the present invention provides a dihalopropene compound(herein-after referred to as the present compound) of the generalformula:

[0008] wherein Z is oxygen, sulfur or NR⁴ (wherein R⁴ is hydrogen orC₁-C₃ alkyl); Y is oxygen, sulfur or NH; X's are independently chlorineor bromine; R², R³ and R¹⁰ are independently halogen, C₁-C₃ haloalkyl orC₁-C₃ alkyl; t is an integer of 0 to 2; and R¹ is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆or Q₇ of the general formula:

[0009] wherein A is an optionally substituted heterocyclic ring group,provided that when A is an optionally substituted heterocyclic ringgroup containing two oxygen atoms and a condensed benzene ring, A isoptionally substituted 1,3-benzodioxolan-2-yl or optionally substituted1,4-benzodioxan-2-yl; B is oxygen, S(O)_(q), NR⁹, C(═G¹)G² or G¹C(═G²);q is an integer of 0 to 2; R⁹ is hydrogen, acetyl or C₁-C₃ alkyl; G¹ andG² are independently oxygen or sulfur; R⁵, R⁶, R⁷, R¹¹ and R¹² areindependently hydrogen, C₁-C₃ alkyl or trifluoromethyl; R¹³ and R¹⁴ areindependently hydrogen, C₁-C₃ alkyl, trifluoromethyl or halogen; p is aninteger of 0 to 6; and s is an integer of 1 to 6.

[0010] The present invention further provides an insecticidal/acaricidalagent containing the above dihalopropene compound as an activeingredient.

[0011] The present invention further provides the following compoundswhich are useful as intermediates for producing some of the presentcompounds:

[0012] a phenol compound which is3,5-dichloro-4-(2-(2-(4-chlorophenyl)-1,3-dioxolan-4yl)ethoxy)phenol;

[0013] compounds of the general formula:

[0014] wherein R⁵, R⁶ and R⁷ are independently hydrogen, C₁-C₃ alkyl ortrifluoromethyl; R¹⁵ is halogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃alkoxy or C₁-C₃ haloalkoxy; R², R³ and R¹⁰ are independently halogen,C₁-C₃ alkyl or C₁-C₃ haloalkyl; t is an integer of 0 to 2; u is aninteger of 1 to 4; w is an integer of 1 to 4; and B¹ is oxygen, S(O)_(q)or NR⁹ wherein R⁹ is hydrogen, acetyl or C₁-C₃ alkyl and q is an integerof 0 to 2;

[0015] compounds of the general formula [I ] wherein R⁵, R⁶ and R⁷ areall hydrogen; and R² and R³ are independently halogen or C₁-C₃ alkyl;and

[0016] 2-(3-methanesulfonyloxypropyloxy)-5-trifluoromethylpyridine.

DETAILED DESCRIPTION OF THE INVENTION

[0017] The variables in the above formulae for the present compounds andtheir intermediates can take the following specific examples.

[0018] Examples of the C₁-C₃ alkyl group represented by R², R³, R⁴, R⁵,R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³ or R¹⁴ are methyl, ethyl, n-propyl andisopropyl.

[0019] Examples of the halogen atom represented by R¹³ or R¹⁴ arefluorine, chlorine, bromine and iodine.

[0020] Examples of the heterocyclic ring in the optionally substitutedheterocyclic ring group represented by A are isoxazole, isothiazole,thiazole, 1,3,4-thiadiazole, pyrrole, furan, thiophene, pyrazole,imidazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,3,4-tetrazole, pyridine,pyridazine, pyrimidine, pyrazine, 1,2,4-triazine, 1,3,5-triazine,indole, benzofuran, thianaphthalene, indazole, benzimidazole,benzotriazole, benzisoxazole, benzoxazole, benzothiazole, quinoline,isoquinoline, quinoxaline, quinazole, piperidine, piperazine,tetrahydrofuran, tetrahydropyran, pyrazoline, phthalimide, dioxane,dioxolane and benzodioxolane.

[0021] Examples of the substituent on the optionally substitutedheterocyclic ring group represented by A are those of the generalformula: (R⁸)_(r) (wherein R⁸ is halogen, nitro, cyano, C₁-C₄ alkyl,C₁-C₃ haloalkyl, C₁-C₄ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃haloalkylthio, C₁-C₂ alkylsulfinyl, C₁-C₂ alkylsulfonyl, C₁-C₂haloalkylsulfinyl C₁-C₂ haloalkylsulfonyl, C₂-C₄ alkenyl, C₂-C₄haloalkenyl, C₂-C₄ alkynyl, C₂-C₄ haloalkynyl, amino, dimethylamino,acetamido, acetyl, haloacetyl, formyl, carboxyl, methoxycarbonyl, C₃-C₆cycloalkyl, (C₁-C₂ alkyl)aminocarbonyl or [di(C₁-C₂alkyl)amino]carbonyl, or R⁸ is phenyl, benzyl, phenoxy, benzyloxy orpyridyloxy, each of which is optionally substituted with halogen, C₁-C₄alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy or C₁-C₃ haloalkoxy; and r is aninteger of 0 to 7.

[0022] Examples of the halogen atom represented by R⁸ or present in R⁸are fluorine, chlorine, bromine and iodine.

[0023] Examples of the C₁-C₄ alkyl group represented by R⁸ or present inR⁸ are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyland tert-butyl.

[0024] Examples of the C₁-C₃ haloalkyl group represented by R⁸ orpresent in R⁸ are trifluoromethyl, difluoromethyl, bromodifluoromethyl,2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl,1-fluoroethyl, 1-chloroethyl, 1-bromoethyl, 2,2,3,3,3-pentafluoropropyl, 3,3,3-trifluoropropyl, 1-fluoropropyl,2-chloropropyl and 3-bromopropyl.

[0025] Examples of the C₁-C₄ alkoxy group represented by R⁸ or presentin R⁸ are methoxy,ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy,isobutoxy and tertbutoxy.

[0026] Examples of the C₁ -C₃ haloalkoxy group represented by R⁸ orpresent in R⁸ are trifluoromethoxy, difluoromethoxy, bromofluoromethoxy,2-fluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloroethoxy, 2-bromoethoxy,2-chloro-1,1,2-trifluoroethoxy, 2-bromo-1,1,2-trifluoroethoxy,1,1,2,2-tetrafluoroethoxy, 1,2,2,3,3,3-hexafluoropropoxy,3-fluoropropoxy, 3-chloropropoxy, 3-bromopropoxy,2,2,3,3,3-pentafluoropropoxy, 3,3,3-trifluoropropoxy and1,1,2,2,2-pentafluoroethoxy.

[0027] Examples of the C₁-C₃ alkylthio group represented by R⁸ aremethylthio, ethylthio, n-propylthio and isopropylthio.

[0028] Examples of the C₁-C₃ haloalkylthio group represented by R⁸ aretrifluoromethylthio, difluoromethylthio, bromodifluoromethylthio,2,2,2-trifluoroethylthio, 2-chloro- 1,1,2-trifluoroethylthio,2-bromo-1,1,2-trifluoroethylthio, 1,1,2,2-tetrafluoroethylthio,2-chloroethylthio, 2-fluoroethylthio, 2-bromoethylthio,3-fluoropropylthio, 3-chloropropylthio, (3-bromopropyl)thio,2,2,3,3,3-pentafluoropropylthio and 3,3,3-trifluoropropylthio.

[0029] Examples of the C₁-C₂ alkylsulfinyl group represented by R⁸ aremethylsulfinyl and ethylsulfinyl.

[0030] Examples of the C₁-C₂ alkylsulfonyl group represented by R⁸ aremethylsulfonyl and ethylsulfonyl.

[0031] Examples of the C₁-C₂ haloalkylsulfinyl group represented by R⁸are trifluoromethylsulfinyl, 2,2,2-tnfluoroethylsulfinyl andperfluoroethylsulfinyl.

[0032] Examples of the C₁-C₂ haloalkylsulfonyl group represented by R⁸are trifluoromethylsulfonyl, 2,2,2-trifluoroethylsulfonyl andperfluoroethylsulfonyl.

[0033] Examples of the C₂-C₄ alkenyl group represented by R⁸ are vinyl,isopropenyl, 1-propenyl, 2-ethyl- 1-propenyl, 1-methyl-1-propenyl,allyl, 2-methylpropenyl and 2-butenyl.

[0034] Examples of the C₂-C₄ haloalkenyl group represented by R⁸ are2,2-dichloroethenyl, 2,2-dibromoethenyl, 3,3-dichloroallyl,3,3-dibromoallyl, 2,3-dichloroallyl, 2,3-dibromoallyl,2-chloro-2-propenyl, 3-chloro-2-propenyl, 2-bromo-2-propenyl and3-chloro-2-butenyl.

[0035] Examples of the C₂-C₄ alkynyl group represented by R⁸ areethynyl, 1-propynyl, 2-propynyl and 1-methyl-2-propynyl.

[0036] Examples of the C₂-C₄ haloalkynyl group represented by R⁸ arechloroethynyl, bromoethynyl, iodoethynyl, 3-chloro-2-propynyl,3-bromo-2-propynyl, 3-iodo-2-propynyl, 1-methyl-3-chloro-2-propynyl,1-methyl-3-bromo-2-propynyl and 1-methyl-3-iodo-2-propynyl.

[0037] Examples of the haloacetyl group represented by R⁸ aretrifluoromethylacetyl and trichloroacetyl.

[0038] Examples of the C₃-C₆ cycloalkyl group represented by R⁸ arecyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0039] Examples of the C₅-C₆ cycloalkenyl are 1-cyclopentenyl,2-cyclopentenyl, 3-cyclopentenyl, 1-cyclobexenyl, 2-cyclohexenyl and3-cyclohexenyl.

[0040] Examples of the (C₁-C₂ alkyl)aminocarbonyl group represented byR⁸ are methylaminocarbonyl and ethylamino carbonyl.

[0041] Examples of the [di(C₁-C₂ alkyl)amino]carbonyl group representedby R⁸ are dimethylaminocarbonyl, N-methyl-N-ethylaminocarbonyl anddiethylaminocarbonyl.

[0042] The following are preferred examples of the present compound:

[0043] dihalopropene compounds wherein A is a 5- or 6-memberedheterocyclic ring group containing at least one oxygen, sulfur ornitrogen and optionally substituted by (R⁸)_(r) (wherein R⁸ is halogen,nitro, cyano, C₁-C₄ alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy, C₁-C₃haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, C₁-C₂ alkylsulfinyl,C₁-C₂ alkylsulfonyl, C₁-C₂ haloalkylsulfinyl, C₁-C₂ haloalkylsulfonyl,C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₂-C₄ haloalkynyl,amino, dimethylamino, acetamido, acetyl, haloacetyl, formyl, carboxyl,methoxycarbonyl, C₃-C₆ cycloalkyl, (C₁-C₂ alkyl)-aminocarbonyl or[di(C₁-C₂ alkyl)amino]carbonyl, or R⁸ is phenyl, benzyl, phenoxy,benzyloxy or pyridyloxy, each of which is optionally substituted withhalogen, C₁-C₄ alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy or C₁-C₃ haloalkoxy;and r is an integer of 0 to 7);

[0044] dihalopropene compounds wherein A is 2-pyridyl, 3-pyridyl,4-pyridyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl,5-(1,3-thiazolyl), N-(1,2-dihydro-2-oxo)pyridino, 1,3-dioxolanyl,1,4-benzodioxanyl, 2-pyrazyl, 2-benzothiazolyl, 2-benzoxazolyl,2-benzimidazolyl, 2-quinoxalynyl, N-benzimidazolyl, 2-quinolyl,3-quinolyl or N-phthalimido, each of which is optionally substitutedwith (R⁸)_(r) (wherein R⁸ and r are each as defined above);

[0045] dihalopropene compounds wherein R² and R³ are independentlyhalogen or C₁-C₃ alkyl, and t is 0;

[0046] dihalopropene compounds wherein R² and R³ are independentlychlorine, bromine, methyl, ethyl or isopropyl, and t is 0;

[0047] dihalopropene compounds wherein R² and R³ are both chlorine, andt is 0;

[0048] dihalopropene compounds wherein R² is chlorine, R³ is methyl, andt is 0;

[0049] dihalopropene compounds wherein R² is ethyl, R³ is methyl, and tis 0;

[0050] dihalopropene compounds wherein R² and R³ are both bromine, and tis 0;

[0051] dihalopropene compounds wherein R² and R³ are both ethyl, and tis 0;

[0052] dihalopropene compounds wherein R² and R³ are independentlyhalogen or C₁-C₃ alkyl, t is 1 or 2, and R¹⁰ is halogen or C₁-C₃ alkyl;

[0053] dihalopropene compounds wherein R² and R³ are independentlyhalogen or C₁-C₃ alkyl, t is 1 or 2, and R¹⁰ is halogen;

[0054] dihalopropene compounds wherein Y and Z are both oxygen;

[0055] dihalopropene compounds wherein R¹ is Q₁ is 1 to 6, and A is2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, 2-furanyl,3-furanyl, 5-(1,3-thiazolyl), N-(1,2-dihydro-2-oxo)pyridino,1,3-dioxolanyl or N-phthalimido, each of which is optionally substitutedwith (R⁸)_(r) (wherein R⁸ and r are each as defined above);

[0056] dihalopropene compounds wherein R¹ is Q₁, p is 1 to 6, R⁵, R⁶ andR⁷ are all hydrogen, and A is 1,3-dioxolanyl optionally substituted with(R⁸)_(r) (wherein R⁸ and r are each as defined above);

[0057] dihalopropene compounds wherein R¹ is Q₁, p is 1 to 4, R⁵, R⁶ andR⁷ are all hydrogen, and A is 1,3-dioxolanyl optionally substituted with(R⁸)_(r) (wherein R⁸ and r are each as defined above);

[0058] dihalopropene compounds wherein R¹ is Q₂, and A is 2-pyridyl,3-pyridyl 4-pyridyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl,5-(1,3-thiazolyl), 1,3-dioxolanyl or 1,4-benzodioxolanyl, each of whichis optionally substituted with (R⁸)_(r) (wherein R⁸ and r are each asdefined above);

[0059] dihalopropene compounds wherein R¹ is Q₂;

[0060] dihalopropene compounds wherein R¹ is Q₂, and A is 2-pyridyl,3-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl,5-(1,3-thiazolyl), 2-pyradyl, 2-benzothiazolyl, 2-benzoxazolyl,2-benzimidazolyl, 2-quinoxalynyl, N-benzimidazolyl, 2-quinolynyl or3-quinolyl, each of which is optionally substituted with (R⁸)_(r)(wherein R⁸ and r are each as defined above);

[0061] dihalopropene compounds wherein R¹ is Q₂, p is 1 to 4, and A is2-pyridyl optionally substituted with (R⁸)_(r) (wherein R⁸ and r areeach as defined above);

[0062] dihalopropene compounds wherein R¹ is Q₂, p is 1 to 4, R⁵, R⁶ andR⁷ are all hydrogen, and A is 2-pyridyl optionally substituted with(R⁸)_(r) (wherein R⁸ and r are each as defined above);

[0063] dihalopropene compounds wherein R¹ is Q², p is 1 to 4, R⁵, R⁶ andR⁷ are all hydrogen, A is 2-pyridyl optionally substituted with (R⁸)_(r)(wherein R⁸ is halogen or C₁-C₃ haloalkyl and r is as defined above);

[0064] dihalopropene compounds wherein R¹ is Q₂, p is 2 or 3, R⁵, R⁶ andR⁷ are all hydrogen, A is 2-pyridyl optionally substituted with (R⁸)_(r)(wherein R⁸ is halogen or C₁-C₃ haloalkyl and r is as defined above);

[0065] dihalopropene compounds wherein R¹ is Q₂, p is 2 or 3, R⁵, R⁶ andR⁷ are all hydrogen, A is 2-pyridyl optionally substituted with (R⁸)_(r)(wherein R⁸ is halogen or trifluoromethyl and r is as defined above);and

[0066] dihalopropene compounds wherein R^(1 is Q) ₂, p is 2 or 3, R⁵, R⁶and R⁷ are all hydrogen, B is oxygen, A is 2-pyridyl optionallysubstituted with (R⁸)_(r) (wherein R⁸ is halogen or trifluoromethyl andr is as defined above).

[0067] The following are particularly preferred examples of the presentcompound wherein numbers in parentheses are the corresponding compoundnumbers used below.

[0068] (36)3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene;

[0069] (47)3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene;and

[0070] (49) 3,5-Dichloro-4 -(3-(5-tri fluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene.

[0071] The present compounds can be produced, for example, by thefollowing production processes A-H.

[0072] (Production Process A)

[0073] In this process, a compound of the general formula:

[0074] wherein R¹, R², R³, R¹⁰, t, Y and Z are each as defined above, isreacted with a halide compound of the general formula:

L—CH₂CH═CX₂  [IV]

[0075] wherein X is as defined above and L is halogen (e.g., chlorine,bromine, iodine), mesyloxy or tosyloxy.

[0076] The reaction is preferably effected in an inert solvent in thepresence of a suitable base.

[0077] Examples of the solvent that can be used are ketones such asacetone, methyl ethyl ketone and cyclohexanone; ethers such as1,2-dimethoxyethane, tetrahydrofuran, dioxane and dialkyl (e.g., C₁-C₄)ether (e.g., diethyl ether, diisopropyl ether); N,N-di-methylformamide,dimethylsulfoxide, hexamethylphosphoric triamide, sulforane,acetonitrile, nitromethane; halogenated hydrocarbons such asdichloromethane, chloroform, 1,2-dichloroethane and chlorobenzene;hydrocarbons such as toluene, benzene and xylene; and water. Ifnecessary, a mixture of these solvents can be used.

[0078] Examples of the base which can be used are hydroxides of alkalimetals or alkaline earth metals, such as lithium hydroxide, sodiumhydroxide, potassium hydroxide and calcium hydroxide; carbonates ofalkali metals or alkaline earth metals, such as lithium carbonate,potassium carbonate, sodium carbonate and calcium carbonate; hydrides ofalkali metals or alkaline earth metals, such as lithium hydride, sodiumhydride, potassium hydride and calcium hydride; alkali metal alkoxides(e.g., C₁-C₄), such as sodium methoxide, sodium ethoxide and potassiumtert-butoxide; and organic bases such as triethylamine and pyridine. Ifnecessary, catalysts such as ammonium salts (e.g.,triethylbenzylammonium chloride) may be added to the reaction system ata ratio of 0.01 to 1 mole per mole of the compound of the generalformula [III].

[0079] The reaction temperature is usually set within the range of −20°C. to 150° C. or the boiling point of a solvent used in the reaction,preferably −5° C. to 100° C. or the boiling point of a solvent used inthe reaction.

[0080] The molar ratio of the starting materials and bases to be used inthe reaction can be freely determined, but it is favorable to effect thereaction at an equimolar ratio or a ratio closer thereto.

[0081] After completion of the reaction, the reaction mixture issubjected to ordinary post-treatments such as organic solvent extractionand concentration, and the desired compound of the present invention canbe isolated. Further, purification can be carried out, if necessary, byan ordinary technique such as chromatography, distillation orrecrystallization.

[0082] (Production Process B for the present compounds wherein Y isoxygen)

[0083] In this process, a compound of the general formula [III] isreacted with an alcohol compound of the general formula:

HO—CH₂CH═CX₂  [IV]

[0084] wherein X is as defined above.

[0085] The reaction is preferably effected in an inert solvent, ifnecessary, in the presence of a suitable dehydrating agent.

[0086] Examples of the dehydrating agent which can be used aredicyclohexylcarbodiimide, and dialkyl (e.g., C₁-C₄) azodicarboxylates(e.g., diethylazodicarboxylate, diisopropylazodicarboxylate)-trialkyl(e.g. C₁-C₂₀) phosphine or triarylphosphine (e.g., triphenylphosphine,trioctylphosphine, tributylphosphine).

[0087] Examples of the solvent which can be used are hydrocarbons suchas benzene, xylene and toluene; ethers such as diethyl ether,diisopropyl ether, tetrahydrofuran and dioxane; and halogenatedhydrocarbons such as carbon tetrachloride, dichloromethane,chlorobenzene and dichlorobenzene.

[0088] The reaction temperature is usually set within the range of −20°C. to 200° C. or the boiling point of a solvent used in the reaction.

[0089] The molar ratio of the starting materials and dehydrating agentsto be used in the reaction can be freely determined, but it is favorableto effect the reaction at an equimolar ratio or a ratio closer thereto.

[0090] After completion of the reaction, the reaction mixture issubjected to ordinary post-treatments such as organic solvent extractionand concentration, and the desired compound of the present invention canbe isolated. Further, purification can be carried out by an ordinarytechnique such as chromatography, distillation or recrystallization.

[0091] (Production Process C for the present compounds wherein Y isoxygen)

[0092] In this process, an aldehyde compound of the general formula:

[0093] wherein R¹, R², R³, R¹⁰, t and Z are each as defined above, isreacted with carbon tetrachloride or carbon tetrabromide.

[0094] The reaction is preferably effected in an inert solvent in thepresence of a suitable trialkylphosphine or triarylphosphine, and ifnecessary, in the presence of metal zinc.

[0095] Examples of the solvent which can be used are hydrocarbons suchas benzene, xylene and toluene; ethers such as diethyl ether,diisopropyl ether, tetrahydrofuran and dioxane; and halogenatedhydrocarbons (exclusive of carbon tetrabromide and carbon tetrachloride)such as dichloromethane, 1,2-dichloroethane and chlorobenzene.

[0096] The reaction temperature is usually set within the range of −30°C. to 150° C. or the boiling point of a solvent used in the reaction.

[0097] Examples of the trialkyl (e.g. C₁-C₂₀) phosphine ortriarylphosphine are triphenylphosphine and trioctylphosphine. The metalzinc which is used, if necessary, is preferably in dust form.

[0098] The molar ratio of the starting materials and reagents to be usedin the reaction can be freely determined, but the ratio is preferablysuch that carbon tetrabromide or tetrachloride, trialkylphosphine ortriarylphosphine, and zinc are 2 moles, 2 or 4 moles (2 moles when zincis used), and 2 moles, respectively, per mole of the aldehyde compoundof the general formula [VI], or it is favorable to effect the reactionat a ratio closer thereto.

[0099] After completion of the reaction, the reaction mixture issubjected to ordinary post-treatments such as organic solvent extractionand concentration, and the desired compound of the present invention canbe isolated. Further, purification can be carried out by an ordinarytechnique such as chromatography, distillation or recrystallization.

[0100] (Production Process D for the present compounds wherein Y and Zare both oxygen)

[0101] In this process, a compound of the general formula:

[0102] wherein R², R³, R¹⁰, t and X are each as defined above, isreacted with a compound of the general formula:

R¹—L  [VIII]

[0103] wherein R ¹ and L are each as defined above.

[0104] The reaction is preferably effected in an inert solvent in thepresence of a suitable base.

[0105] Examples of the solvent which can be used are ketones such asacetone, methyl ethyl ketone and cyclohexanone; ethers such as1,2-dimethoxyethane, tetrahydrofuran, dioxane and dialkyl (e.g., C₁-C₄)ethers (e.g., diethyl ether, diisopropyl ether); N,N-dimethylformamide,dimethylsulfoxide, hexamethylphosphoric triamide, sulforane,acetonitrile, nitromethane; halogenated hydrocarbons such asdichloromethane, chloroform, 1,2-dichloroethane and chlorobenzene;hydrocarbons such as toluene, benzene and xylene; and water. Ifnecessary, a mixture of these solvents can be used.

[0106] Examples of the base which can be used are hydroxides of alkalimetals or alkaline earth metals, such as lithium hydroxide, sodiumhydroxide, potassium hydroxide and calcium hydroxide; carbonates ofalkali metals or alkaline earth metals, such as lithium carbonate,potassium carbonate, sodium carbonate and calcium carbonate; hydrides ofalkali metals or alkaline earth metals, such as lithium hydride, sodiumhydride, potassium hydride and calcium hydride; alkali metal alkoxides(e.g., C₁-C₄) such as sodium methoxide, sodium ethoxide and potassiumtert-butoxide; organic bases such as triethylamine and pyridine. Ifnecessary, catalysts such as ammonium salts (e.g.,triethylbenzylammonium chloride) may be added to the reaction system ata ratio of 0.01 to 1 mole per mole of the compound of the generalformula [VII].

[0107] The reaction temperature is usually set within the range of −20°C. to 150° C. or the boiling point of a solvent used in the reaction,preferably −5° C. to 100° C. or the boiling point of a solvent used inthe reaction.

[0108] The molar ratio of the starting materials and dehydrating agentsto be used in the reaction can be freely determined, but it is favorableto effect the reaction at an equimolar ratio or a ratio closer thereto.

[0109] After completion of the reaction, the reaction mixture issubjected to ordinary post-treatments such as organic solvent extractionand concentration, and the desired compound of the present invention canbe isolated. Further, purification can be carried out by an ordinarytechnique such as chromatography, distillation or recrystallization.

[0110] (Production Process E for the present compounds wherein Y and Zare both oxygen)

[0111] In this process, a compound of the general formula [VII] isreacted with an alcohol compound of the general formula:

R¹—OH  [IX]

[0112] wherein R¹ is as defined above.

[0113] The reaction is preferably effected in an inert solvent, ifnecessary, in the presence of a suitable dehydrating agent.

[0114] Examples of the dehydrating agent which can be used aredicyclohexylcarbodiimide, and dialkyl (e c., C₁-C₄) azodicarboxylates(e.g., diethylazodicarboxylate, diisopropylazodicarboxylate)-trialkyl(e.g., C₁-C₂₀) phosphine or triarylphosphine (e.g., triphenylphosphine,trioctylphosphine, tributylphosphine).

[0115] Examples of the solvent which can be used are hydrocarbons suchas benzene, xylene and toluene; ethers such as diethyl ether,diisopropyl ether, tetrahydrofuran and dioxane; and halogenatedhydrocarbons such as carbon tetrachloride, dichloromethane,chlorobenzene and dichlorobenzene.

[0116] The reaction temperature is usually set within the range of −20°C. to 200° C. or the boiling point of a solvent used in the reaction.

[0117] The molar ratio of the materials and dehydrating agents to beused in the reaction can be freely determined, but it is favorable toeffect the reaction at an equimolar ratio or a ratio closer thereto.

[0118] After completion of the reaction, the reaction mixture issubjected to ordinary post-treatments such as organic solvent extractionand concentration, and the desired compound of the present invention canbe isolated. Further, purification can be carried out by an ordinarytechnique such as chromatography, distillation or recrystallization.

[0119] (Production Process F for the present compounds wherein Y and Zare both oxygen, R¹ is Q₂ or Q₃, and B is B¹ (wherein B¹ is oxygen,sulfur or NR⁹ [wherein R⁹ is as defined above]))

[0120] In this process, a compound of the general formula:

[0121] wherein B¹, R², R³, R⁵, R⁶, R⁷, R¹⁰, p, t and X are each asdefined above, is reacted with a compound of the general formula:

[0122] wherein A, R¹¹, R¹², L and s are each as defined above.

[0123] The reaction is preferably effected in an inert solvent in thepresence of a suitable base.

[0124] Examples of the solvent which can be used are ketones such asacetone, methyl ethyl ketone and cyclohexanone; ethers such as1,2-dimethoxyethane, tetrahydrofuran, dioxane and dialkyl (e.g., C₁-C₄)ethers (e.g., diethyl ether, diisopropyl ether); N,N-dimethylformamide,dimethylsulfoxide, hexamethylphosphoric triamide, sulforane,acetonitrile, nitromethane; halogenated hydrocarbons such asdichloromethane, chloroform, 1,2-dichloroethane and chlorobenzene;hydrocarbons such as toluene, benzene and xylene; and water. Ifnecessary, a mixture of these solvents can be used.

[0125] Examples of the base which can be used are hydroxides of alkalimetals or alkaline earth metals, such as lithium hydroxide, sodiumhydroxide, potassium hydroxide and calcium hydroxide; carbonates ofalkali metals or alkaline earth metals, such as lithium carbonate,potassium carbonate, sodium carbonate and calcium carbonate; hydrides ofalkali metals or alkaline earth metals, such as lithium hydride, sodiumhydride, potassium hydride and calcium hydride; alkali metal alkoxides(e.g., C₁-C₄) such as sodium methoxide, sodium ethoxide and potassiumtert-butoxide; organic bases such as triethylamine and pyridine. Ifnecessary, catalysts such as ammonium salts (e.g.,triethylbenzylammonium chloride) may be added to the reaction system ata ratio of 0.01 to 1 mole per mole of the compound of the generalformula [X].

[0126] The reaction temperature is usually set within the range of −20°C. to 150° C. or the boiling point of a solvent used in the reaction,preferably −5° C. to 100° C. or the boiling point of a solvent used inthe reaction.

[0127] The molar ratio of the starting materials and dehydrating agentsto be used in the reaction can be freely determined, but it is favorableto effect the reaction at an equimolar ratio or a ratio closer thereto.

[0128] After completion of the reaction, the reaction mixture issubjected to ordinary post-treatments such as organic solvent extractionand concentration, and the desired compound of the present invention canbe isolated. Further, purification can be carried out by an ordinarytechnique such as chromatography, distillation or recrystallization.

[0129] (Production Process G for the present compounds wherein Y, Z andB are all oxygen and R¹ is Q₂, Q₃, Q₆ or Q₇)

[0130] In this process, an alcohol compound of the general formula:

[0131] wherein R², R³, R¹⁰, R⁵, R⁶, R⁷, p, t and X are each as definedabove, is reacted with compound Q₂₁, Q₃₁, Q₆₁ or Q₇₁ of the generalformula:

[0132] wherein R¹¹, R¹², R¹³, R¹⁴, and s are each as defined above.

[0133] The reaction is preferably effected in an inert solvent, ifnecessary, in the presence of a suitable dehydrating agent.

[0134] Examples of the dehydrating agent which can be used aredicyclohexylcarbodiimide, and dialkyl (e.g., C₁-C₄) azodicarboxylates(e.g., diethylazodicarboxylate, diisopropylazodicarboxylate)-trialkyl(e-,g., C₁-C₂₀) phosphine or triarylphosphine (e.g., triphenylphosphine,trioctylphosphine, tributylphosphine).

[0135] Examples of the solvent which can be used are hydrocarbons suchas D benzene, xylene and toluene; ethers such as diethyl ether,diisopropyl ether, tetrahydrofuran and dioxane;, and halogenatedhydrocarbons such as carbon tetrachloride, dichloromethane,chlorobenzene and dichlorobenzene.

[0136] The reaction temperature is usually set within the range of −20°C. to 200° C. or the boiling point of a solvent used in the reaction.

[0137] The molar ratio of the materials and dehydrating agents to beused in the reaction can be freely determined, but it is favorable toeffect the reaction at an equimolar ratio or a ratio closer thereto.

[0138] After completion of the reaction, the reaction mixture issubjected to ordinary post-treatments such as organic solvent extractionand concentration, and the desired compound of the present invention canbe isolated. Further, purification can be carried out by an ordinarytechnique such as chromatography, distillation or recrystallization.

[0139] (Production Process H for the present compounds wherein Y and Zare both oxygen and R¹ is Q₂, Q₃, Q₆ or Q₇)

[0140] In this process, a compound of the general formula:

[0141] wherein R², R³, R⁵, R⁶, R⁷, R¹⁰, X, L, p and t are each asdefined above, is reacted with compound Q₂₂, Q₃₂, Q₆₂ or Q₇₂ of thegeneral formula:

[0142] wherein R¹¹, R¹²,R¹³, R¹⁴, A, B and s are each as defined above.

[0143] The reaction is preferably effected in an inert solvent in thepresence of a suitable base.

[0144] Examples of the solvent which can be used are ketones such asacetone, methyl ethyl ketone and cyclohexanone; ethers such as1,2-dimethoxyethane, tetrahydrofuran, dioxane and dialkyl (e.g., C₁-C₄)ethers (e.g., diethyl ether, diisopropyl ether); N,N-dimethylformamide,dimethylsulfoxide, hexamethylphosphoric triamide, sulforane,acetonitrile, nitromethane; halogenated hydrocarbons such asdichloromethane, chloroform, 1,2-dichloroethane and chlorobenzene;hydrocarbons such as toluene, benzene and xylene; and water. Ifnecessary, a mixture of these solvents can be used.

[0145] Examples of the base which can be used are hydroxides of alkalimetals or alkaline earth metals, such as lithium hydroxide, sodiumhydroxide, potassium hydroxide and calcium hydroxide; carbonates ofalkali metals or alkaline earth metals, such as lithium carbonate,potassium carbonate, sodium carbonate and calcium carbonate; hydrides ofalkali metals or alkaline earth metals, such as lithium hydride, sodiumhydride, potassium hydride and calcium hydride; alkali metal alkoxides(e.g., C₁-C₄) such as sodium methoxide, sodium ethoxide and potassiumtert-butoxide; organic bases such as triethylamine and pyridine. Ifnecessary, catalysts such as ammonium salts (e.g.,triethylbenzylammonium chloride) may be added to the reaction system ata ratio of 0.01 to 1 mole per mole of the compound of the generalformula [XIV].

[0146] The reaction temperature is usually set within the range of −20°C. to 150° C. or the boiling point of a solvent used in the reaction,preferably −5° C. to 100° C. or the boiling point of a solvent used inthe reaction.

[0147] The molar ratio of the starting materials and dehydrating agentsto be used in the reaction can be freely determined, but it is favorableto effect the reaction at an equimolar ratio or a ratio closer thereto.

[0148] After completion of the reaction, the reaction mixture issubjected to ordinary post-treatments such as organic solvent extractionand concentration, and the desired compound of the present invention canbe isolated. Further, purification can be carried out by an ordinarytechnique such as chromatography, distillation or recrystallization.

[0149] When the present compound has an asymmetry carbon atom, it is tobe construed to include its optically active isomers ((+)-form and(−)-form) having biological activity and their mixtures at any ratio.When the present compound exhibits geometrical isomerism, it is to beconstrued to include its geometrical isomers (cis-form and transform)and their mixtures at any ratio.

[0150] The following are typical examples of the present compound(wherein R¹is as shown in Tables 1 to 46), which are not to be construedto limit the scope of the present invention.

TABLE 1

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 H 2H H H 0 5-CH₃ 2 H H H 1 5-CH₃ 2 H H H 2 5-CH₃ 2 H H H 3 5-CH₃ 2 H H H 45-CH₃ 2 H H H 5 5-CH₃ 2 H H H 6 5-CH₃ 2 H H H 0 5-CH₂OCH₃ 2 H H H 15-CH₂OCH₃ 2 H H H 2 5-CH₂OCH₃ 2 H H H 3 5-CH₂OCH₃ 2 H H H 4 5-CH₂OCH₃ 2H H H 0 5-CH₂CH₃ 2 H H H 1 5-CH₂CH₃ 2 H H H 2 5-CH₂CH₃ 2 H H H 35-CH₂CH₃ 2 H H H 4 5-CH₂CH₃ 2 H H H 5 5-CH₂CH₃ 2 H H H 6 5-CH₂CH₃ 2 H HCH₃ 0 H 2 H H CH₃ 0 5-CH₃ 2 H H H 0 5-CHO 2 H H H 1 5-CHO 2 H H H 25-CHO 2 H H H 3 5-CHO 2 H H H 4 5-CHO 2 H H H 5 5-CHO 2 H H H 6 5-CHO 2H H H 0 5-NO₂ 2 H H H 1 5-NO₂ 2 H H H 2 5-NO₂ 2 H H H 3 5-NO₂ 2 H H H 45-NO₂ 2 H H H 5 5-NO₂ 2 H H H 6 5-NO₂ 2 H H H 0 3-CO₂CH₃ 3 H H H 0 H 3 HH H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3 HH H 0 2-CH₃ 3 H H H 1 2-CH₃ 3 H H H 2 2-CH₃ 3 H H H 3 2-CH₃ 3 H H H 42-CH₃ 3 H H H 5 2-CH₃ 3 H H H 6 2-CH₃ 3 H H H 0 2,5-(CH₃)₂ 3 H H H 12,5-(CH₃)₂ 3 H H H 2 2,5-(CH₃)₂ 3 H H H 3 2,5-(CH₃)₂ 3 H H H 42,5-(CH₃)₂ 3 H H H 5 2,5-(CH₃)₂ 3 H H H 6 2,5-(CH₃)₂ 3 H H H 02,4-(CH₃)₂ 3 H H H 1 2,4-(CH₃)₂ 3 H H H 2 2,4-(CH₃)₂ 3 H H H 32,4-(CH₃)₂ 3 H H H 4 2,4-(CH₃)₂ 3 H H H 5 2,4-(CH₃)₂ 3 H H H 62,4-(CH₃)₂

[0151] TABLE 2

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) B 2 H H H 1 HCOO 2 H H H 2 H COO 2 H H H 3 H COO 2 H H H 1 5-CH₃ COO 2 H H H 1 5-C₂H₅COO 2 H H H 1 5-Br COO 2 H H H 2 5-CH₃ COO 2 H H H 2 5-C₂H₅ COO 2 H H H2 5-Br COO 2 H H H 3 5-CH₃ COO 2 H H H 3 5-C₂H₅ COO 2 H H H 3 5-CH₃ COO3 H H H 1 H COO 3 H H H 2 H COO 3 H H H 3 H COO

[0152] TABLE 3

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 H 2H H H 0 5-CH₃ 2 H H H 1 5-CH₃ 2 H H H 2 5-CH₃ 2 H H H 3 5-CH₃ 2 H H H 45-CH₃ 2 H H H 5 5-CH₃ 2 H H H 6 5-CH₃ 2 H H H 0 5-Cl 2 H H H 1 5-Cl 2 HH H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 5 5-Cl 2 H H H 6 5-Cl 2H H H 0 5-Br 2 H H H 1 5-Br 2 H H H 2 5-Br 2 H H H 3 5-Br 2 H H H 4 5-Br2 H H H 5 5-Br 2 H H H 6 5-Br 2 H H H 0 5-NO₂ 2 H H H 1 5-NO₂ 2 H H H 25-NO₂ 2 H H H 3 5-NO₂ 2 H H H 4 5-NO₂ 2 H H H 5 5-NO₂ 2 H H H 6 5-NO₂ 2H H H 0 5-NH₂ 2 H H H 1 5-NH₂ 2 H H H 2 5-NH₂ 2 H H H 3 5-NH₂ 2 H H H 45-NH₂ 2 H H H 5 5-NH₂ 2 H H H 6 5-NH₂ 2 H H H 0 5-NHCOCH₃ 2 H H H 15-NHCOCH₃ 2 H H H 2 5-NHCOCH₃ 2 H H H 3 5-NHCOCH₃ 2 H H H 4 5-NHCOCH₃ 2H H H 5 5-NHCOCH₃ 2 H H H 6 5-NHCOCH₃ 2 H H H 0 5-NHCOCF₃ 2 H H H 15-NHCOCF₃ 2 H H H 2 5-NHCOCF₃ 2 H H H 3 5-NHCOCF₃ 2 H H H 4 5-NHCOCF₃ 2H H H 5 5-NHCOCF₃ 2 H H H 6 5-NHCOCF₃ 2 H H CH₃ 0 3-CH₃ 2 H H CH₃ 0 5-Cl2 H H CH₃ 0 5-Br 2 H H CH₂CH₃ 0 H 2 H H H 0 3-CH₃ 2 H H H 1 3-CH₃ 2 H HH 0 5-NH₂ 2 H H H 2 3-CH₃ 2 H H H 3 3-CH₃ 2 H H H 4 3-CH₃ 2 H H H 53-CH₃ 2 H H H 6 3-CH₃ 2 H H H 0 4-Br 2 H H H 1 4-Br 2 H H H 2 4-Br 2 H HH 3 4-Br 2 H H H 4 4-Br 2 H H H 5 4-Br 2 H H H 6 4-Br 3 H H H 0 H 3 H HH 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3 H HCH₃ 0 H 3 H H CH₃ 0 2,5-(CH₃)₂

[0153] TABLE 4

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) F 3 S H H H0 2-CH₃ O 2 SO₂ H H H 0 H S 2 SO₂ H H H 1 H S 2 SO₂ H H H 2 H S 2 SO₂ HH H 3 H S 2 SO₂ H H H 4 H S 2 SO₂ H H H 5 H S 2 SO₂ H H H 6 H S 2 COO HH H 2 H S 2 COO H H H 3 H S 2 COO H H H 4 H S 3 COO H H H 2 H S 3 COO HH H 3 H S 3 COO H H H 4 H S 2 COO H H H 2 5-CH₃ S 2 COO H H H 3 5-CH₃ S2 COO H H H 4 5-CH₃ S

[0154] TABLE 5

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 H

[0155] TABLE 6

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 6 H

[0156] TABLE 7

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 3 H H H 0 H 3H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3H H H 0 5-Cl 3 H H H 1 5-Cl 3 H H H 2 5-Cl 3 H H H 3 5-Cl 3 H H H 4 5-Cl3 H H H 5 5-Cl 3 H H H 6 5-Cl 3 H H H 0 5-Br 3 H H H 1 5-Br 3 H H H 25-Br 3 H H H 3 5-Br 3 H H H 4 5-Br 3 H H H 5 5-Br 3 H H H 6 5-Br 5 H H H0 H 5 H H H 1 H 5 H H H 2 H 5 H H H 3 H 5 H H H 4 H 5 H H H 5 H 5 H H H6 H 5 H H H 0 3-Cl 5 H H H 1 3-Cl 5 H H H 2 3-Cl 5 H H H 3 3-Cl 5 H H H4 3-Cl 5 H H H 5 3-Cl 5 H H H 6 3-Cl 5 H H H 0 3-Br 5 H H H 1 3-Br 5 H HH 2 3-Br 5 H H H 3 3-Br 5 H H H 4 3-Br 5 H H H 5 3-Br 5 H H H 6 3-Br 4 HH H 0 H 4 H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4 HH H 6 H 4 H H H 0 3,5-(CH₃)₂

[0157] TABLE 8

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 3 H H H 0 H 3H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3H H H 0 5-Cl 3 H H H 1 5-Cl 3 H H H 2 5-Cl 3 H H H 3 5-Cl 3 H H H 4 5-Cl3 H H H 5 5-Cl 3 H H H 6 5-Cl 3 H H H 0 5-Br 3 H H H 1 5-Br 3 H H H 25-Br 3 H H H 3 5-Br 3 H H H 4 5-Br 3 H H H 5 5-Br 3 H H H 6 5-Br

[0158] TABLE 9

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 4 H H H 0 H 4H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4 H H H 6 H 4H H H 0 2-Cl 4 H H H 1 2-Cl 4 H H H 2 2-Cl 4 H H H 3 2-Cl 4 H H H 4 2-Cl4 H H H 5 2-Cl 4 H H H 6 2-Cl 4 H H H 0 2-Br 4 H H H 1 2-Br 4 H H H 22-Br 4 H H H 3 2-Br 4 H H H 4 2-Br 4 H H H 5 2-Br 4 H H H 6 2-Br 5 H H H0 H 5 H H H 1 H 5 H H H 2 H 5 H H H 3 H 5 H H H 4 H 5 H H H 5 H 5 H H H6 H 5 H H H 0 2-Cl 5 H H H 1 2-Cl 5 H H H 2 2-Cl 5 H H H 3 2-Cl 5 H H H4 2-Cl 5 H H H 5 2-Cl 5 H H H 6 2-Cl 5 H H H 0 2-Br 5 H H H 1 2-Br 5 H HH 2 2-Br 5 H H H 3 2-Br 5 H H H 4 2-Br 5 H H H 5 2-Br 5 H H H 6 2-Br 5 HH H 1 4-CH₃ 5 H H CH₃ 0 4-CH₃ 2 H H CH₃ 0 H

[0159] TABLE 10

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 1 H H H 0 H 1H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H 1H H H 0 2-CH₂CH₃ 1 H H H 1 2-CH₂CH₃ 1 H H H 2 2-CH₂CH₃ 1 H H H 32-CH₂CH₃ 1 H H H 4 2-CH₂CH₃ 1 H H H 5 2-CH₂CH₃ 1 H H H 6 2-CH₂CH₃ 1 H HH 0 2,5-(CH₃)₂ 1 H H H 1 2,5-(CH₃)₂ 1 H H H 2 2,5-(CH₃)₂ 1 H H H 32,5-(CH₃)₂ 1 H H H 4 2,5-(CH₃)₂ 1 H H H 5 2,5-(CH₃)₂ 1 H H H 62,5-(CH₃)₂ 1 H H H 0 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 1 2,4-(CH₃)₂, 3-CH₂CH₃1 H H H 2 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 3 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 42,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 5 2,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 62,4-(CH₃)₂, 3-CH₂CH₃ 1 H H H 0 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 1 2,4-(CH₃)₂,3-COCH₃ 1 H H H 2 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 3 2,4-(CH₃)₂, 3-COCH₃ 1 HH H 4 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 5 2,4-(CH₃)₂, 3-COCH₃ 1 H H H 62,4-(CH₃)₂, 3-COCH₃ 1 H H H 0 2-COCH₃ 1 H H H 1 2-COCH₃ 1 H H H 22-COCH₃ 1 H H H 3 2-COCH₃ 1 H H H 4 2-COCH₃ 1 H H H 5 2-COCH₃ 1 H H H 62-COCH₃ 1 H H H 0 2-CHO 1 H H H 1 2-CHO 1 H H H 2 2-CHO 1 H H H 3 2-CHO1 H H H 4 2-CHO 1 H H H 5 2-CHO 1 H H H 6 2-CHO 2 H H CH₃ 0 2,4-(CH₃)₂ 2H H CH₃ 0 H 2 H H CH₃ 0 1-CH₃ 3 H H CH₃ 0 1-CH₃ 3 H H H 0 H 3 H H H 1 H3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 2 H H H 0 H2 H H H 1 1-CH₃ 2 H H H 2 1-CH₃ 2 H H H 3 1-CH₃ 2 H H H 4 1-CH₃ 2 H H H5 1-CH₃ 2 H H H 6 1-CH₃ 2 H H H 0 3,5-(CH₃)₂ 2 H H H 1 3,5-(CH₃)₂ 2 H HH 2 3,5-(CH₃)₂ 2 H H H 3 3,5-(CH₃)₂ 2 H H H 4 3,5-(CH₃)₂ 2 H H H 53,5-(CH₃)₂ 2 H H H 6 3,5-(CH₃)₂ 2 H H H 0 3,4,5-(CH₃)₃ 2 H H H 13,4,5-(CH₃)₃ 2 H H H 2 3,4,5-(CH₃)₃ 2 H H H 3 3,4,5-(CH₃)₃ 2 H H H 43,4,5-(CH₃)₃ 2 H H H 5 3,4,5-(CH₃)₃ 2 H H H 6 3,4,5-(CH₃)₃ 2 H H H 03,4-(C₂H₅)₂, 5-CH₃ 2 H H H 1 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H 2 3,4-(C₂H₅)₂,5-CH₃ 2 H H H 3 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H 4 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H5 3,4-(C₂H₅)₂, 5-CH₃ 2 H H H 6 3,4-(C₂H₅)₂, 5-CH₃

[0160] TABLE 11

Bonding position at heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 5-Cl2 H H H 1 5-Cl 2 H H H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 55-Cl 2 H H H 6 5-Cl 2 H H H 0 5-Br 2 H H H 1 5-Br 2 H H H 2 5-Br 2 H H H3 5-Br 2 H H H 4 5-Br 2 H H H 5 5-Br 2 H H H 6 5-Br 2 H H H 0 5-Cl 2 H HH 1 5-Cl 2 H H H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 5 5-Cl 2 HH H 6 5-Cl 2 H H H 0 5-Br 2 H H H 1 5-Br 2 H H H 2 5-Br 2 H H H 3 5-Br 2H H H 4 5-Br 2 H H H 5 5-Br 2 H H H 6 5-Br

[0161] TABLE 12

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 2 O H H H 05-CH₃ 2 O H H H 1 5-CH₃ 2 O H H H 2 5-CH₃ 2 O H H H 3 5-CH₃ 2 O H H H 45-CH₃ 2 O H H H 5 5-CH₃ 2 O H H H 6 5-CH₃ 2 O H H H 0 5-CF₃ 2 O H H H 15-CF₃ 2 O H H H 2 5-CF₃ 2 O H H H 3 5-CF₃ 2 O H H H 4 5-CF₃ 2 O H H H 55-CF₃ 2 O H H H 6 5-CF₃ 2 O H H H 0 5-Cl 2 O H H H 1 5-Cl 2 O H H H 25-Cl 2 O H H H 3 5-Cl 2 O H H H 4 5-Cl 2 O H H H 5 5-Cl 2 O H H H 6 5-Cl2 O H H H 0 5-Br 2 O H H H 1 5-Br 2 O H H H 2 5-Br 2 O H H H 3 5-Br 2 OH H H 4 5-Br 2 O H H H 5 5-Br 2 O H H H 6 5-Br 2 S H H H 0 5-CH₃ 2 S H HH 1 5-CH₃ 2 S H H H 2 5-CH₃ 2 S H H H 3 5-CH₃ 2 S H H H 4 5-CH₃ 2 S H HH 5 5-CH₃ 2 S H H H 6 5-CH₃ 2 S H H H 0 5-CF₃ 2 S H H H 1 5-CF₃ 2 S H HH 2 5-CF₃ 2 S H H H 3 5-CF₃ 2 S H H H 4 5-CF₃ 2 S H H H 5 5-CF₃ 2 S H HH 6 5-CF₃ 2 S H H H 0 5-Cl 2 S H H H 1 5-Cl 2 S H H H 2 5-Cl 2 S H H H 35-Cl 2 S H H H 4 5-Cl 3 S H H H 5 5-Cl 3 S H H H 6 5-Cl 3 S H H H 0 5-Br3 S H H H 1 5-Br 3 S H H H 2 5-Br 3 S H H H 3 5-Br 3 S H H H 4 5-Br 2 SH H H 5 5-Br 2 S H H H 6 5-Br

[0162] TABLE 13

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 1 H H H 0 H 1H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H 1H H H 0 3-CH₃ 1 H H H 1 3-CH₃ 1 H H H 2 3-CH₃ 1 H H H 3 3-CH₃ 1 H H H 43-CH₃ 1 H H H 5 3-CH₃ 1 H H H 6 3-CH₃ 1 H H H 0 4-CH₃ 1 H H H 1 4-CH₃ 1H H H 2 4-CH₃ 1 H H H 3 4-CH₃ 1 H H H 4 4-CH₃ 1 H H H 5 4-CH₃ 1 H H H 64-CH₃ 1 H H H 0 4-Br 1 H H H 1 4-Br 1 H H H 2 4-Br 1 H H H 3 4-Br 1 H HH 4 4-Br 1 H H H 5 4-Br 1 H H H 6 4-Br 1 H H H 0 4-I 1 H H H 1 4-I 1 H HH 2 4-I 1 H H H 3 4-I 1 H H H 4 4-I 1 H H H 5 4-I 1 H H H 6 4-I 1 H H H0 3,5-(CH₃)₂ 1 H H H 1 3,5-(CH₃)₂ 1 H H H 2 3,5-(CH₃)₂ 1 H H H 33,5-(CH₃)₂ 1 H H H 4 3,5-(CH₃)₂ 1 H H H 5 3,5-(CH₃)₂ 1 H H H 63,5-(CH₃)₂ 1 H H H 0 3-CH₃, 4-Br 1 H H H 1 3-CH₃, 4-Br 1 H H H 2 3-CH₃,4-Br 1 H H H 3 3-CH₃, 4-Br 1 H H H 4 3-CH₃, 4-Br 1 H H H 5 3-CH₃, 4-Br 1H H H 6 3-CH₃, 4-Br 1 H H H 0 3,5-(CH₃)₂, 4-Br 1 H H H 1 3,5-(CH₃)₂,4-Br 1 H H H 2 3,5-(CH₃)₂, 4-Br 1 H H H 3 3,5-(CH₃)₂, 4-Br 1 H H H 43,5-(CH₃)₂, 4-Br 1 H H H 5 3,5-(CH₃)₂, 4-Br 1 H H H 6 3,5-(CH₃)₂, 4-Br 4H H H 0 H

[0163] TABLE 14

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 4 NH H H H 05-CH₃, 1-CH₃, 2-C₆H₅ 5 NH H H H 0 1-CH₂CH₃ 5 NH H H H 1 1-CH₂CH₃ 5 NH HH H 2 1-CH₂CH₃ 5 NH H H H 3 1-CH₂CH₃ 5 NH H H H 4 1-CH₂CH₃ 5 NH H H H 51-CH₂CH₃ 5 NH H H H 6 1-CH₂CH₃

[0164] TABLE 15

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 1 H H H 0 H 1H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H 1H H H 0 2-CH₃ 1 H H H 1 2-CH₃ 1 H H H 2 2-CH₃ 1 H H H 3 2-CH₃ 1 H H H 42-CH₃ 1 H H H 5 2-CH₃ 1 H H H 6 2-CH₃ 1 H H H 1 2-CH₂CH₃ 1 H H H 02-CH₂CH₃ 1 H H H 2 2-CH₂CH₃ 1 H H H 3 2-CH₂CH₃ 1 H H H 4 2-CH₂CH₃ 1 H HH 5 2-CH₂CH₃ 1 H H H 6 2-CH₂CH₃ 1 H H H 0 2-CH₂CH₂CH₃ 1 H H H 12-CH₂CH₂CH₃ 1 H H H 2 2-CH₂CH₂CH₃ 1 H H H 3 2-CH₂CH₂CH₃ 1 H H H 42-CH₂CH₂CH₃ 1 H H H 5 2-CH₂CH₂CH₃ 1 H H H 6 2-CH₂CH₂CH₃ 1 H H H 02-CH(CH₃)₂ 1 H H H 1 2-CH(CH₃)₂ 1 H H H 2 2-CH(CH₃)₂ 1 H H H 32-CH(CH₃)₂ 1 H H H 4 2-CH(CH₃)₂ 1 H H H 5 2-CH(CH₃)₂ 1 H H H 62-CH(CH₃)₂ 1 H H H 0 2-CH(CH₃)₂ 1 H H H 1 4,5-Cl₂ 1 H H H 2 4,5-Cl₂ 1 HH H 3 4,5-Cl₂ 1 H H H 4 4,5-Cl₂ 1 H H H 5 4,5-Cl₂ 1 H H H 6 4,5-Cl₂ 1 HH H 0 2,4,5-Cl₃ 1 H H H 1 2,4,5-Cl₃ 1 H H H 2 2,4,5-Cl₃ 1 H H H 32,4,5-Cl₃ 1 H H H 4 2,4,5-Cl₃ 1 H H H 5 2,4,5-Cl₃ 1 H H H 6 2,4,5-Cl₃ 1H H H 0 4,5-Br₂ 1 H H H 1 4,5-Br₂ 1 H H H 2 4,5-Br₂ 1 H H H 3 4,5-Br₂ 1H H H 4 4,5-Br₂ 1 H H H 5 4,5-Br₂ 1 H H H 6 4,5-Br₂ 1 H H H 0 2,4,5-Br₃1 H H H 1 2,4,5-Br₃ 1 H H H 2 2,4,5-Br₃ 1 H H H 3 2,4,5-Br₃ 1 H H H 42,4,5-Br₃ 1 H H H 5 2,4,5-Br₃ 1 H H H 6 2,4,5-Br₃ 1 H H H 0 4,5-(CN)₂ 1H H H 1 4,5-(CN)₂ 1 H H H 2 4,5-(CN)₂ 1 H H H 3 4,5-(CN)₂ 1 H H H 44,5-(CN)₂ 1 H H H 5 4,5-(CN)₂ 1 H H H 6 4,5-(CN)₂ 1 H H CH₃ 0 H 1 H H H0 2-NO₂ 1 H H H 1 2-NO₂ 1 H H H 2 2-NO₂ 1 H H H 3 2-NO₂ 1 H H H 4 2-NO₂1 H H H 5 2-NO₂ 1 H H H 6 2-NO₂ 4 H H H 0 H 4 H H H 1 H 4 H H H 2 H 5 HH H 0 4-CH₃ 2 H H H 0 H

[0165] TABLE 16

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 2 S H H H 0H 2 S H H H 1 H 2 S H H H 2 H 2 S H H H 3 H 2 S H H H 4 H 2 S H H H 5 H2 S H H H 6 H 2 S H H H 0 1-CH₃ 2 S H H H 1 1-CH₃ 2 S H H H 2 1-CH₃ 2 SH H H 3 1-CH₃ 2 S H H H 4 1-CH₃ 2 S H H H 5 1-CH₃ 2 S H H H 6 1-CH₃

[0166] TABLE 17

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 4 H H H 03,6-Cl₂ 4 H H H 1 3,6-Cl₂ 4 H H H 2 3,6-Cl₂ 4 H H H 3 3,6-Cl₂ 4 H H H 43,6-Cl₂ 4 H H H 5 3,6-Cl₂ 4 H H H 6 3,6-Cl₂

[0167] TABLE 18

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 3 H H H 0 H 3H H H 1 H 3 H H H 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H

[0168] TABLE 19

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 1 H H H 0 H 1H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H 4H H H 0 H 4 H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4H H H 6 H

[0169] TABLE 20

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 3 S H H H 0H 3 S H H H 1 H 3 S H H H 2 H 3 S H H H 3 H 3 S H H H 4 H 3 S H H H 5 H3 S H H H 6 H 5 S H H H 0 1-CH₃ 5 S H H H 1 1-CH₃ 5 S H H H 2 1-CH₃ 5 SH H H 3 1-CH₃ 5 S H H H 4 1-CH₃ 5 S H H H 5 1-CH₃ 5 S H H H 6 1-CH₃

[0170] TABLE 21

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 1 H H H 0 H 1H H H 1 H 1 H H H 2 H 1 H H H 3 H 1 H H H 4 H 1 H H H 5 H 1 H H H 6 H

[0171] TABLE 22

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 5 S H H H 01-CH₃ 5 S H H H 1 1-CH₃ 5 S H H H 2 1-CH₃ 5 S H H H 3 1-CH₃ 5 S H H H 41-CH₃ 5 S H H H 5 1-CH₃ 5 S H H H 6 1-CH₃

[0172] TABLE 23

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 4 H H H 0 H 4H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4 H H H 6 H 4H H H 0 6-CH₃ 4 H H H 1 6-CH₃ 4 H H H 2 6-CH₃ 4 H H H 3 6-CH₃ 4 H H H 46-CH₃ 4 H H H 5 6-CH₃ 4 H H H 6 6-CH₃ 4 H H H 0 2,6-Cl₂

[0173] TABLE 24

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 2 O H H H 64-CH₃ 4 O H H H 0 2,6-(CH₃)₂ 4 O H H H 1 2,6-(CH₃)₂ 4 O H H H 22,6-(CH₂)₃ 4 O H H H 3 2,6-(CH₃)₂ 4 O H H H 4 2,6-(CH₃)₂ 4 O H H H 52,6-(CH₃)₂ 4 O H H H 6 2,6-(CH₃)₂ 2 S H H H 0 H 2 S H H H 1 H 2 S H H H2 H 2 S H H H 3 H 2 S H H H 4 H 2 S H H H 5 H 2 S H H H 6 H 2 NH H H H 1H 2 NH H H H 0 H 2 O H H H 2 5-CF₃ 2 O H H H 3 5-CF₃ 5 O H H H 2 5-CF₃ 5O H H H 3 5-CF₃ 2 NH H H H 2 H 2 NH H H H 3 H 2 NH H H H 4 H 3 NH H H H5 H 3 NH H H H 6 H 3 S H H H 0 4-CH₃ 3 S H H H 1 4-CH₃ 3 S H H H 2 4-CH₃3 S H H H 3 4-CH₃ 3 S H H H 4 4-CH₃ 2 O H H H 0 H 2 O H H H 1 H 2 O H HH 2 H 2 O H H H 3 H 2 O H H H 4 H 2 O H H H 5 H 2 O H H H 6 H 2 O H H H0 4,6-(CH₃)₂ 2 O H H H 1 4,6-(CH₃)₂ 2 O H H H 2 4,6-(CH₃)₂ 2 O H H H 34,6-(CH₃)₂ 2 O H H H 4 4,6-(CH₃)₂ 2 O H H H 5 4,6-(CH₃)₂ 2 O H H H 64,6-(CH₃)₂ 2 NH H H H 0 4,6-(CH₃)₂ 2 NH H H H 1 4,6-(CH₃)₂ 2 NH H H H 24,6-(CH₃)₂ 2 NH H H H 3 4,6-(CH₃)₂ 2 NH H H H 4 4,6-(CH₃)₂ 2 NH H H H 54,6-(CH₃)₂ 2 NH H H H 6 4,6-(CH₃)₂ 2 O H H H 0 4-CH₃ 2 O H H H 1 4-CH₃ 2O H H H 2 4-CH₃ 2 O H H H 3 4-CH₃ 2 O H H H 4 4-CH₃ 2 O H H H 5 4-CH₃ 2S H H H 5 4-CH₃ 2 S H H H 6 4-CH₃ 2 NH H H H 0 4-CH₃ 2 NH H H H 1 4-CH₃2 NH H H H 2 4-CH₃ 2 NH H H H 3 4-CH₃ 2 NH H H H 4 4-CH₃ 2 NH H H H 54-CH₃ 2 NH H H H 6 4-CH₃ 2 S H H H 0 4,6-(CH₃)₂ 2 S H H H 1 4,6-(CH₃)₂ 2S H H H 2 4,6-(CH₃)₂ 2 S H H H 3 4,6-(CH₃)₂ 2 S H H H 4 4,6-(CH₃)₂ 2 S HH H 5 4,6-(CH₃)₂ 2 S H H H 0 4,6-Cl₂ 2 S H H H 6 4,6-(CH₃)₂ 2 S H H H 14,6-Cl₂ 2 S H H H 2 4,6-Cl₂ 2 S H H H 3 4,6-Cl₂ 2 S H H H 4 4,6-Cl₂ 2 SH H H 5 4,6-Cl₂ 2 S H H H 6 4,6-Cl₂ 4 NH H H H 0 H 4 NH H H H 1 H 4 NH HH H 2 H 4 NH H H H 3 H 4 NH H H H 4 H 4 NH H H H 5 H 4 NH H H H 6 H 2 NHH H H 0 5-Br 2 NH H H H 1 5-Br 2 NH H H H 2 5-Br 2 NH H H H 3 5-Br 2 NHH H H 4 5-Br 2 NH H H H 5 5-Br 2 NH H H H 6 5-Br 4 NH H H H 0 2,6-(CH₃)₂4 NH H H H 1 2,6-(CH₃)₂ 4 NH H H H 2 2,6-(CH₃)₂ 4 NH H H H 3 2,6-(CH₃)₂4 NH H H H 4 2,6-(CH₃)₂ 4 NH H H H 5 2,6-(CH₃)₂ 4 NH H H H 6 2,6-(CH₃)₂2 NH H H H 0 4-Cl, 6-CH₃ 2 NH H H H 1 4-Cl, 6-CH₃ 2 NH H H H 2 4-Cl,6-CH₃ 2 NH H H H 3 4-Cl, 6-CH₃ 2 NH H H H 4 4-Cl, 6-CH₃ 2 NH H H H 54-Cl, 6-CH₃ 2 NH H H H 6 4-Cl, 6-CH₃ 2 NH H H H 0 4-OCH₃, 6-CH₃ 2 NH H HH 1 4-OCH₃, 6-CH₃ 2 NH H H H 2 4-OCH₃, 6-CH₃ 2 NH H H H 3 4-OCH₃, 6-CH₃2 NH H H H 4 4-OCH₃, 6-CH₃ 2 NH H H H 5 4-OCH₃, 6-CH₃ 2 NH H H H 64-OCH₃, 6-CH₃ 2 O H H H 0 4,6-(OCH₃)₂ 2 O H H H 1 4,6-(OCH₃)₂ 2 O H H H2 4,6-(OCH₃)₂ 2 O H H H 3 4,6-(OCH₃)₂ 2 O H H H 4 4,6-(OCH₃)₂ 2 O H H H5 4,6-(OCH₃)₂ 2 O H H H 6 4,6-(OCH₃)₂ 2 NH H H H 0 4,6-(OCH₃)₂ 2 NH H HH 1 4,6-(OCH₃)₂ 2 NH H H H 2 4,6-(OCH₃)₂ 2 NH H H H 4 4,6-(OCH₃)₂ 2 NH HH H 3 4,6-(OCH₃)₂ 2 NH H H H 2 5-CF₃ 2 NH H H H 3 5-CF₃ 5 NH H H H 25-CF₃ 5 NH H H H 3 5-CF₃ 2 NH H H H 5 4,6-(OCH₃)₂ 2 NH H H H 64,6-(OCH₃)₂ 2 S H H H 0 4,6-(OCH₃)₂ 2 S H H H 1 4,6-(OCH₃)₂ 2 S H H H 24,6-(OCH₃)₂ 2 S H H H 3 4,6-(OCH₃)₂ 2 S H H H 4 4,6-(OCH₃)₂ 2 S H H H 54,6-(OCH₃)₂ 2 S H H H 6 4,6-(OCH₃)₂ 5 NH H H H 0 4,6-Cl₂ 5 NH H H H 14,6-Cl₂ 2 S H H H 2 5-CF₃ 2 S H H H 3 5-CF₃ 5 S H H H 2 5-CF₃ 5 S H H H3 5-CF₃

[0174] TABLE 25

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 2 H H H 0 H 2H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H 65-CH₃ 2 H H H 0 5-CH₃ 2 H H H 1 5-CH₃ 2 H H H 2 5-CH₃ 2 H H H 3 5-CH₃ 2H H H 4 5-CH₃ 2 H H H 5 5-CH₃ 2 H H H 6 5-CH₃ 2 H H H 0 6-CH₃ 2 H H H 16-CH₃ 2 H H H 2 6-CH₃ 2 H H H 3 6-CH₃ 2 H H H 4 6-CH₃ 2 H H H 5 6-CH₃ 2H H H 6 6-CH₃ 2 H H H 0 3-CH₃ 2 H H H 1 3-CH₃ 2 H H H 2 3-CH₃ 2 H H H 33-CH₃ 2 H H H 4 3-CH₃ 2 H H H 5 3-CH₃ 2 H H H 6 3-CH₃ 2 H H H 0 5-CH₃ 2H H H 1 5-CH₃ 2 H H H 2 5-CH₃ 2 H H H 3 5-CH₃ 2 H H H 4 5-CH₃ 2 H H H 55-CH₃ 2 H H H 6 5-CH₃ 2 H H H 0 3-OCH₃ 2 H H H 1 3-OCH₃ 2 H H H 2 3-OCH₃2 H H H 3 3-OCH₃ 2 H H H 4 3-OCH₃ 2 H H H 5 3-OCH₃ 2 H H H 6 3-OCH₃ 2 HH H 0 6-OCH₂CH₂CH₃ 2 H H H 1 6-OCH₂CH₂CH₃ 2 H H H 2 6-OCH₂CH₂CH₃ 2 H H H3 6-OCH₂CH₂CH₃ 2 H H H 4 6-OCH₂CH₂CH₃ 2 H H H 5 6-OCH₂CH₂CH₃ 2 H H H 66-OCH₂CH₂CH₃

[0175] TABLE 26

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 2 O H H H 0H 2 O H H H 1 H 2 O H H H 2 H 2 O H H H 3 H 2 O H H H 4 H 2 O H H H 5 H2 O H H H 6 H 2 NH H H H 0 H 2 NH H H H 1 H 2 NH H H H 2 H 2 NH H H H 3H 2 NH H H H 4 H 2 NH H H H 5 H 2 NH H H H 6 H 2 S H H H 0 H 2 S H H H 1H 2 S H H H 2 H 2 S H H H 3 H 2 S H H H 4 H 2 S H H H 5 H 2 S H H H 6 H2 O H H H 0 6-Cl 2 O H H H 1 6-Cl 2 O H H H 2 6-Cl 2 O H H H 3 6-Cl 2 OH H H 4 6-Cl 2 O H H H 5 6-Cl 2 O H H H 6 6-Cl 2 NH H H H 0 6-Cl 2 NH HH H 1 6-Cl 2 NH H H H 2 6-Cl 2 NH H H H 3 6-Cl 2 NH H H H 4 6-Cl 2 NH HH H 5 6-Cl 2 NH H H H 6 6-Cl 2 S H H H 0 6-Cl 2 S H H H 1 6-Cl 2 S H H H2 6-Cl 2 S H H H 3 6-Cl 2 S H H H 4 6-Cl 2 S H H H 5 6-Cl 2 S H H H 66-Cl

[0176] TABLE 27

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 3 NH H H H 0H 3 NH H H H 1 H 3 NH H H H 2 H 3 NH H H H 3 H 3 NH H H H 4 H 3 NH H H H5 H 3 NH H H H 6 H

[0177] TABLE 28

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 2 O H H H 04,6-Cl₂ 2 O H H H 1 4,6-Cl₂ 2 O H H H 2 4,6-Cl₂ 2 O H H H 3 4,6-Cl₂ 2 OH H H 4 4,6-Cl₂ 2 O H H H 5 4,6-Cl₂ 2 O H H H 6 4,6-Cl₂ 2 S H H H 04,6-Cl₂ 2 S H H H 1 4,6-Cl₂ 2 S H H H 2 4,6-Cl₂ 2 S H H H 3 4,6-Cl₂ 2 SH H H 4 4,6-Cl₂ 2 S H H H 5 4,6-Cl₂ 2 S H H H 6 4,6-Cl₂ 2 NH H H H 04,6-Cl₂ 2 NH H H H 2 4,6-Cl₂ 2 NH H H H 1 4,6-Cl₂ 2 NH H H H 3 4,6-Cl₂ 2NH H H H 4 4,6-Cl₂ 2 NH H H H 5 4,6-Cl₂ 2 NH H H H 6 4,6-Cl₂ 2 O H H H 04-Cl, 6-OCH₃ 2 O H H H 1 4-Cl, 6-OCH₃ 2 O H H H 2 4-Cl, 6-OCH₃ 2 O H H H3 4-Cl, 6-OCH₃ 2 O H H H 4 4-Cl, 6-OCH₃ 2 O H H H 5 4-Cl, 6-OCH₃ 2 O H HH 6 4-Cl, 6-OCH₃ 2 NH H H H 1 4-Cl, 6-OCH₃ 2 NH H H H 0 4-Cl, 6-OCH₃ 2NH H H H 2 4-Cl, 6-OCH₃ 2 NH H H H 3 4-Cl, 6-OCH₃ 2 NH H H H 4 4-Cl,6-OCH₃ 2 NH H H H 5 4-Cl, 6-OCH₃ 2 NH H H H 6 4-Cl, 6-OCH₃ 2 S H H H 04-Cl, 6-OCH₃ 2 S H H H 1 4-Cl, 6-OCH₃ 2 S H H H 2 4-Cl, 6-OCH₃ 2 S H H H3 4-Cl, 6-OCH₃ 2 S H H H 4 4-Cl, 6-OCH₃ 2 S H H H 5 4-Cl, 6-OCH₃ 2 S H HH 6 4-Cl, 6-OCH₃

[0178] TABLE 29

Bonding position of heterocyclic ring R⁵ R⁶ R⁷ p (R⁸)_(r) 3 H H H 0 H 3H H H 0 6-Cl 3 H H H 0 6-Br 3 H H H 0 6-I 3 H H H 0 6-CH₃ 3 H H H 06-CF₃ 3 H H CH₃ 0 H 3 H H H 0 2-CH₃ 3 H H H 0 4-(CH₂)₃CH₃ 3 H H H 0 2-Cl3 H H H 0 4-Br 3 H H H 0 2,6-Cl₂ 3 H H H 0 2-Cl, 6-CH₃ 3 H H H 0 5,6-Cl₂3 H H H 0 2,6-(OCH₃)₂ 3 H H H 0 2-SCH₃ 3 H H H 0 5-CH₃ 3 H H H 1 H 3 H HH 2 H 3 H H H 3 H 3 H H H 4 H 3 H H H 5 H 3 H H H 6 H 3 H H H 1 5-CH₃ 3H H H 2 5-CH₃ 3 H H H 3 5-CH₃ 3 H H H 4 5-CH₃ 3 H H H 5 5-CH₃ 3 H H H 65-CH₃ 3 H H CH₃ 1 H 3 H H CH₃ 2 H 3 H H CH₃ 4 H 3 H H CH₃ 5 H 3 H H CH₃3 H 3 H H CH₃ 6 H 3 H H CH₃ 1 2-CH₃ 3 H H CH₃ 2 2-CH₃ 3 H H CH₃ 3 2-CH₃3 H H CH₃ 4 2-CH₃ 3 H H CH₃ 5 2-CH₃ 3 H H CH₃ 6 2-CH₃ 3 H H CH₃ 1 6-CH₃3 H H CH₃ 2 6-CH₃ 3 H H CH₃ 3 6-CH₃ 3 H H H 4 6-CH₃ 3 H H H 6 6-CH₃ 3 HH H 5 6-CH₃ 3 H H H 1 6-Cl 3 H H H 2 6-Cl 3 H H H 3 6-Cl 3 H H H 4 6-Cl3 H H H 5 6-Cl 3 H H H 6 6-Cl 3 H H H 1 6-Br 3 H H H 2 6-Br 3 H H H 36-Br 3 H H H 4 6-Br 3 H H H 5 6-Br 3 H H H 6 6-Br 3 H H H 1 6-I 3 H H H2 6-I 3 H H H 3 6-I 3 H H H 4 6-I 3 H H H 5 6-I 3 H H H 6 6-I 3 H H H 16-CF₃ 3 H H H 2 6-CF₃ 3 H H H 3 6-CF₃ 3 H H H 4 6-CF₃ 3 H H H 5 6-CF₃ 3H H H 6 6-CF₃ 3 H H H 1 2-Cl 3 H H H 2 2-Cl 3 H H H 3 2-Cl 3 H H H 42-Cl 3 H H H 5 2-Cl 3 H H H 6 2-Cl 3 H H H 1 5-Br 3 H H H 2 5-Br 3 H H H3 5-Br 3 H H H 4 5-Br 3 H H H 5 5-Br 3 H H H 6 5-Br 3 H H H 1 2-Cl,6-CH₃ 3 H H H 2 2-Cl, 6-CH₃ 3 H H H 4 2-Cl, 6-CH₃ 3 H H H 3 2-Cl, 6-CH₃3 H H H 5 2-Cl, 6-CH₃ 3 H H H 6 2-Cl, 6-CH₃ 3 H H H 1 2,6-Cl₂ 3 H H H 22,6-Cl₂ 3 H H H 3 2,6-Cl₂ 3 H H H 4 2,6-Cl₂ 3 H H H 5 2,6-Cl₂ 3 H H H 62,6-Cl₂ 3 H H H 1 5,6-Cl₂ 3 H H H 2 5,6-Cl₂ 3 H H H 3 5,6-Cl₂ 3 H H H 45,6-Cl₂ 3 H H H 5 5,6-Cl₂ 3 H H H 6 5,6-Cl₂ 3 H H H 1 5,6-(OCH₃)₂ 3 H HH 2 5,6-(OCH₃)₂ 3 H H H 3 5,6-(OCH₃)₂ 3 H H H 4 5,6-(OCH₃)₂ 3 H H H 55,6-(OCH₃)₂ 3 H H H 6 5,6-(OCH₃)₂ 3 H H H 1 2-SCH₃ 3 H H H 2 2-SCH₃ 3 HH H 3 2-SCH₃ 3 H H H 4 2-SCH₃ 3 H H H 5 2-SCH₃ 3 H H H 6 2-SCH₃ 2 H H H0 H 2 H H H 1 H 2 H H H 2 H 2 H H H 3 H 2 H H H 4 H 2 H H H 5 H 2 H H H6 H 2 H H H 0 6-CH₃ 2 H H H 1 6-CH₃ 2 H H H 2 6-CH₃ 2 H H H 3 6-CH₃ 2 HH H 4 6-CH₃ 2 H H H 5 6-CH₃ 2 H H H 6 6-CH₃ 2 H H H 0 6-Cl 2 H H H 16-Cl 2 H H H 2 6-Cl 2 H H H 3 6-Cl 2 H H H 4 6-Cl 2 H H H 5 6-Cl 2 H H H6 6-Cl 2 H H H 0 5-CF₃ 2 H H H 1 5-CF₃ 2 H H H 2 5-CF₃ 2 H H H 3 5-CF₃ 2H H H 4 5-CF₃ 2 H H H 5 5-CF₃ 2 H H H 0 5-Cl 2 H H H 6 5-CF₃ 2 H H H 15-Cl 2 H H H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 5 5-Cl 2 H H H6 5-Cl 2 H H H 0 3-Cl 2 H H H 1 3-Cl 2 H H H 2 3-Cl 2 H H H 3 3-Cl 2 H HH 4 3-Cl 2 H H H 5 3-Cl 2 H H H 6 3-Cl 2 H H H 0 6-F 2 H H H 1 6-F 2 H HH 2 6-F 2 H H H 3 6-F 2 H H H 4 6-F 2 H H H 5 6-F 2 H H H 6 6-F 2 H H H0 6-Br 2 H H H 1 6-Br 2 H H H 2 6-Br 2 H H H 3 6-Br 2 H H H 4 6-Br 2 H HH 5 6-Br 2 H H H 6 6-Br 3 H H H 0 6-Cl 3 H H H 1 6-Cl 3 H H H 2 6-Cl 3 HH H 3 6-Cl 3 H H H 4 6-Cl 3 H H H 5 6-Cl 3 H H H 6 6-Cl 3 H H H 0 5-Cl 3H H H 1 5-Cl 3 H H H 2 5-Cl 2 H H H 3 5-Cl 2 H H H 4 5-Cl 2 H H H 5 5-Cl2 H H H 6 5-Cl 2 H H H 0 5-Br 2 H H H 1 5-Br 2 H H H 2 5-Br 2 H H H 35-Br 2 H H H 4 5-Br 2 H H H 5 5-Br 2 H H H 6 5-Br 2 H H H 0 3,5-(CF₃)₂ 2H H H 1 3,5-(CF₃)₂ 2 H H H 2 3,5-(CF₃)₂ 2 H H H 3 3,5-(CF₃)₂ 2 H H H 43,5-(CF₃)₂ 2 H H H 5 3,5-(CF₃)₂ 2 H H H 6 3,5-(CF₃)₂ 2 H H H 04,5-(CF₃)₂ 2 H H H 1 4,5-(CF₃)₂ 2 H H H 2 4,5-(CF₃)₂ 2 H H H 34,5-(CF₃)₂ 2 H H H 4 4,5-(CF₃)₂ 2 H H H 5 4,5-(CF₃)₂ 2 H H H 64,5-(CF₃)₂ 2 H H H 0 3,5-Cl₂ 2 H H H 1 3,5-Cl₂ 2 H H H 2 3,5-Cl₂ 2 H H H3 3,5-Cl₂ 2 H H H 4 3,5-Cl₂ 2 H H H 5 3,5-Cl₂ 2 H H H 6 3,5-Cl₂ 2 H H H0 3-Cl, 5-CF₃ 2 H H H 1 3-Cl, 5-CF₃ 2 H H H 2 3-Cl, 5-CF₃ 2 H H H 33-Cl, 5-CF₃ 2 H H H 4 3-Cl, 5-CF₃ 2 H H H 5 3-Cl, 5-CF₃ 2 H H H 6 3-Cl,5-CF₃ 2 H H H 0 3,5,6-F₃ 2 H H H 0 3,5,6-F₃, 4CH₃ 2 H H H 0 5-CN, 6-Cl 4H H H 0 H 4 H H H 1 H 4 H H H 2 H 4 H H H 3 H 4 H H H 4 H 4 H H H 5 H 4H H H 6 H 4 H H H 0 2,3,5,6-F₄ 4 H H CH₃ 0 H 4 H H CH₃ 1 H 4 H H CH₃ 2 H4 H H CH₃ 3 H 4 H H CH₃ 4 H 4 H H CH₃ 5 H 4 H H CH₃ 6 H 2 H H CH₃ 0 H 2H H CH₃ 1 H 2 H H CH₃ 2 H 2 H H CH₃ 3 H 2 H H CH₃ 4 H 2 H H CH₃ 5 H 2 HH CH₃ 6 H

[0179] TABLE 30

Bonding position of heterocyclic ring B R⁵ R⁶ R⁷ p (R⁸)_(r) 2 O H H H 0H 2 O H H H 1 H 2 O H H H 2 H 2 O H H H 3 H 2 O H H H 4 H 2 O H H H 5 H2 O H H H 6 H 2 NH H H H 0 H 2 NH H H H 1 H 2 NH H H H 2 H 2 NH H H H 3H 2 NH H H H 4 H 2 NH H H H 5 H 2 NH H H H 6 H 2 S H H H 0 H 2 S H H H 1H 2 S H H H 2 H 2 S H H H 3 H 2 S H H H 4 H 2 S H H H 5 H 2 S H H H 6 H2 O H H H 0 4-CH₃ 2 O H H H 1 4-CH₃ 2 O H H H 2 4-CH₃ 2 O H H H 3 4-CH₃2 O H H H 4 4-CH₃ 2 O H H H 5 4-CH₃ 2 O H H H 6 4-CH₃ 2 NH H H H 0 4-CH₃2 NH H H H 1 4-CH₃ 2 NH H H H 2 4-CH₃ 2 NH H H H 3 4-CH₃ 2 NH H H H 44-CH₃ 2 NH H H H 5 4-CH₃ 2 NH H H H 6 4-CH₃ 2 S H H H 0 4-CH₃ 2 S H H H1 4-CH₃ 2 S H H H 2 4-CH₃ 2 S H H H 3 4-CH₃ 2 S H H H 4 4-CH₃ 2 S H H H5 4-CH₃ 2 S H H H 6 4-CH₃ 2 O H H H 0 6-CH₃ 2 O H H H 1 6-CH₃ 2 O H H H2 6-CH₃ 2 O H H H 3 6-CH₃ 2 O H H H 4 6-CH₃ 2 O H H H 5 6-CH₃ 2 O H H H6 6-CH₃ 2 NH H H H 0 6-CH₃ 2 NH H H H 1 6-CH₃ 2 NH H H H 2 6-CH₃ 2 NH HH H 3 6-CH₃ 2 NH H H H 4 6-CH₃ 2 COO H H H 1 H 2 COO H H H 2 H 2 COO H HH 3 H 3 COO H H H 1 H 3 COO H H H 2 H 3 COO H H H 3 H 4 COO H H H 1 H 4COO H H H 2 H 4 COO H H H 3 H 2 COO H H H 2 3-Cl, 5-CF₃ 2 COO H H H 33-Cl, 5-CF₃ 2 COO H H H 2 5-CF₃ 2 COO H H H 3 5-CF₃ 3 COO H H H 2 6-CF₃3 COO H H H 3 6-CF₃ 3 COO H H H 2 6-CH₃ 3 COO H H H 3 6-CH₃ 3 COO H H H2 6-Cl 3 COO H H H 3 6-Cl 3 COO H H H 2 6-Br 3 COO H H H 3 6-Br 3 COO HH H 2 6-I 3 COO H H H 3 6-I 2 NH H H H 5 6-CH₃ 2 NH H H H 6 6-CH₃ 2 S HH H 0 6-CH₃ 2 S H H H 1 6-CH₃ 2 S H H H 2 6-CH₃ 2 S H H H 3 6-CH₃ 2 S HH H 4 6-CH₃ 2 S H H H 5 6-CH₃ 2 S H H H 6 6-CH₃ 2 O H H H 0 6-Cl 2 O H HH 1 6-Cl 2 O H H H 2 6-Cl 2 O H H H 3 6-Cl 2 O H H H 4 6-Cl 2 O H H H 56-Cl 2 O H H H 6 6-Cl 2 S H H H 0 6-Cl 2 S H H H 1 6-Cl 2 S H H H 2 6-Cl2 S H H H 3 6-Cl 2 S H H H 4 6-Cl 2 S H H H 5 6-Cl 2 S H H H 6 6-Cl 2 NHH H H 0 6-Cl 2 NH H H H 1 6-Cl 2 NH H H H 2 6-Cl 2 NH H H H 3 6-Cl 2 NHH H H 4 6-Cl 2 NH H H H 5 6-Cl 2 NH H H H 6 6-Cl 2 O H H H 0 5-Cl 2 O HH H 1 5-Cl 2 O H H H 2 5-Cl 2 O H H H 3 5-Cl 2 O H H H 4 5-Cl 2 O H H H5 5-Cl 2 O H H H 6 5-Cl 2 NH H H H 0 5-Cl 2 NH H H H 1 5-Cl 2 NH H H H 25-Cl 2 NH H H H 3 5-Cl 2 NH H H H 4 5-Cl 2 NH H H H 5 5-Cl 2 NH H H H 65-Cl 2 S H H H 0 5-Cl 2 S H H H 1 5-Cl 2 S H H H 2 5-Cl 2 S H H H 3 5-Cl2 S H H H 4 5-Cl 2 S H H H 5 5-Cl 2 S H H H 6 5-Cl 2 N—CH₃ H H H 0 5-Cl2 N—CH₃ H H H 1 5-Cl 2 N—CH₃ H H H 2 5-Cl 2 N—CH₃ H H H 3 H 2 N—CH₃ H HH 4 H 2 N—CH₃ H H H 5 H 2 N—CH₃ H H H 6 H 2 NH H H H 0 3-CH₃ 2 NH H H H1 3-CH₃ 2 NH H H H 2 3-CH₃ 2 NH H H H 3 3-CH₃ 2 NH H H H 4 3-CH₃ 2 NH HH H 5 3-CH₃ 2 NH H H H 6 3-CH₃ 2 S H H H 0 3-CH₃ 2 S H H H 1 3-CH₃ 2 S HH H 2 3-CH₃ 2 S H H H 3 3-CH₃ 2 S H H H 4 3-CH₃ 2 S H H H 5 3-CH₃ 2 S HH H 6 3-CH₃ 2 O H H H 0 3-CH₃ 2 O H H H 1 3-CH₃ 2 O H H H 2 3-CH₃ 2 O HH H 3 3-CH₃ 2 O H H H 4 3-CH₃ 2 O H H H 5 3-CH₃ 2 O H H H 6 3-CH₃ 2 NH HH H 0 5-CH₃ 2 NH H H H 1 5-CH₃ 2 NH H H H 2 5-CH₃ 2 NH H H H 3 5-CH₃ 2NH H H H 4 5-CH₃ 2 NH H H H 5 5-CH₃ 2 NH H H H 6 5-CH₃ 2 O H H H 0 5-CH₃2 O H H H 1 5-CH₃ 2 O H H H 2 5-CH₃ 2 O H H H 3 5-CH₃ 2 O H H H 4 5-CH₃2 O H H H 5 5-CH₃ 2 O H H H 6 5-CH₃ 2 S H H H 0 5-CH₃ 2 S H H H 1 5-CH₃2 S H H H 2 5-CH₃ 2 S H H H 3 5-CH₃ 2 S H H H 4 5-CH₃ 2 S H H H 5 5-CH₃2 S H H H 6 5-CH₃ 2 NH H H H 0 5-Br 2 NH H H H 1 5-Br 2 NH H H H 2 5-Br2 NH H H H 3 5-Br 2 NH H H H 4 5-Br 2 NH H H H 5 5-Br 2 NH H H H 6 5-Br2 O H H H 0 5-Br 2 O H H H 1 5-Br 2 O H H H 2 5-Br 2 O H H H 3 5-Br 2 OH H H 4 5-Br 2 O H H H 5 5-Br 2 O H H H 6 5-Br 2 S H H H 0 5-Br 2 S H HH 1 5-Br 2 S H H H 2 5-Br 2 S H H H 3 5-Br 2 S H H H 4 5-Br 2 S H H H 55-Br 2 S H H H 6 5-Br 2 S H H H 0 5-Br 2 S H H H 1 5-Br 2 S H H H 2 5-Br2 S H H H 3 5-Br 2 S H H H 4 5-Br 2 S H H H 5 5-Br 2 S H H H 6 5-Br 2 NHH H H 0 4,6-(CH₃)₂ 2 NH H H H 1 4,6-(CH₃)₂ 2 NH H H H 2 4,6-(CH₃)₂ 2 NHH H H 3 4,6-(CH₃)₂ 2 NH H H H 4 4,6-(CH₃)₂ 2 NH H H H 5 4,6-(CH₃)₂ 2 NHH H H 6 4,6-(CH₃)₂ 2 O H H H 0 4,6-(CH₃)₂ 2 O H H H 1 4,6-(CH₃)₂ 2 O H HH 2 4,6-(CH₃)₂ 2 O H H H 3 4,6-(CH₃)₂ 2 O H H H 4 4,6-(CH₃)₂ 2 O H H H 54,6-(CH₃)₂ 2 O H H H 6 4,6-(CH₃)₂ 2 S H H H 0 4,6-(CH₃)₂ 2 S H H H 14,6-(CH₃)₂ 2 S H H H 2 4,6-(CH₃)₂ 2 S H H H 3 4,6-(CH₃)₂ 2 S H H H 44,6-(CH₃)₂ 2 S H H H 5 4,6-(CH₃)₂ 2 S H H H 6 4,6-(CH₃)₂ 2 NH H H H 03-Cl, 5-CF₃ 2 NH H H H 1 3-Cl, 5-CF₃ 2 NH H H H 2 3-Cl, 5-CF₃ 2 NH H H H3 3-Cl, 5-CF₃ 2 NH H H H 4 3-Cl, 5-CF₃ 2 NH H H H 5 3-Cl, 5-CF₃ 2 NH H HH 6 3-Cl, 5-CF₃ 2 O H H H 0 3-Cl, 5-CF₃ 2 O H H H 1 3-Cl, 5-CF₃ 2 O H HH 2 3-Cl, 5-CF₃ 2 O H H H 3 3-Cl, 5-CF₃ 2 O H H H 4 3-Cl, 5-CF₃ 2 O H HH 5 3-Cl, 5-CF₃ 2 O H H H 6 3-Cl, 5-CF₃ 2 S H H H 0 3-Cl, 5-CF₃ 2 S H HH 1 3-Cl, 5-CF₃ 2 S H H H 2 3-Cl, 5-CF₃ 2 S H H H 3 3-Cl, 5-CF₃ 2 S H HH 4 3-Cl, 5-CF₃ 2 S H H H 5 3-Cl, 5-CF₃ 2 S H H H 6 3-Cl, 5-CF₃ 2 NH H HH 0 5-NO₂ 2 NH H H H 1 5-NO₂ 2 NH H H H 0 3-Br, 5-CF₃ 2 NH H H H 1 3-Br,5-CF₃ 2 NH H H H 2 3-Br, 5-CF₃ 2 NH H H H 3 3-Br, 5-CF₃ 2 NH H H H 43-Br, 5-CF₃ 2 NH H H H 5 3-Br, 5-CF₃ 2 NH H H H 6 3-Br, 5-CF₃ 2 O H H H0 3-Br, 5-CF₃ 2 O H H H 1 3-Br, 5-CF₃ 2 O H H H 2 3-Br, 5-CF₃ 2 O H H H3 3-Br, 5-CF₃ 2 O H H H 4 3-Br, 5-CF₃ 2 O H H H 5 3-Br, 5-CF₃ 2 O H H H6 3-Br, 5-CF₃ 2 S H H H 0 3-Br, 5-CF₃ 2 S H H H 1 3-Br, 5-CF₃ 2 S H H H2 3-Br, 5-CF₃ 2 S H H H 3 3-Br, 5-CF₃ 2 S H H H 4 3-Br, 5-CF₃ 2 S H H H5 3-Br, 5-CF₃ 2 S H H H 6 3-Br, 5-CF₃ 2 NH H H H 0 3-F, 5-CF₃ 2 NH H H H1 3-F, 5-CF₃ 2 NH H H H 2 3-F, 5-CF₃ 2 NH H H H 3 3-F, 5-CF₃ 2 NH H H H4 3-F, 5-CF₃ 2 NH H H H 5 3-F, 5-CF₃ 2 NH H H H 6 3-F, 5-CF₃ 2 O H H H 03-F, 5-CF₃ 2 O H H H 1 3-F, 5-CF₃ 2 O H H H 2 3-F, 5-CF₃ 2 O H H H 33-F, 5-CF₃ 2 O H H H 4 3-F, 5-CF₃ 2 O H H H 5 3-F, 5-CF₃ 2 O H H H 63-F, 5-CF₃ 2 S H H H 0 3-F, 5-CF₃ 2 S H H H 1 3-F, 5-CF₃ 2 S H H H 23-F, 5-CF₃ 2 S H H H 3 3-F, 5-CF₃ 2 S H H H 4 3-F, 5-CF₃ 2 S H H H 53-F, 5-CF₃ 2 S H H H 6 3-F, 5-CF₃ 2 NH H H H 2 5-NO₂ 2 NH H H H 3 5-NO₂2 NH H H H 4 5-NO₂ 2 NH H H H 5 5-NO₂ 2 NH H H H 6 5-NO₂ 2 O H H H 05-NO₂ 2 O H H H 1 5-NO₂ 2 O H H H 2 5-NO₂ 2 O H H H 3 5-NO₂ 2 O H H H 45-NO₂ 2 O H H H 5 5-NO₂ 2 O H H H 6 5-NO₂ 2 S H H H 0 5-NO₂ 2 S H H H 15-NO₂ 2 S H H H 2 5-NO₂ 2 S H H H 3 5-NO₂ 2 S H H H 4 5-NO₂ 2 S H H H 55-NO₂ 2 S H H H 6 5-NO₂ 2 NH H H H 0 3-NO₂, 5-Br 2 NH H H H 1 3-NO₂,5-Br 2 NH H H H 2 3-NO₂, 5-Br 2 NH H H H 3 3-NO₂, 5-Br 2 NH H H H 43-NO₂, 5-Br 2 NH H H H 5 3-NO₂, 5-Br 2 NH H H H 6 3-NO₂, 5-Br 2 O H H H0 3-NO₂, 5-Br 2 O H H H 1 3-NO₂, 5-Br 2 O H H H 2 3-NO₂, 5-Br 2 O H H H3 3-NO₂, 5-Br 2 O H H H 4 3-NO₂, 5-Br 2 O H H H 5 3-NO₂, 5-Br 2 O H H H6 3-NO₂, 5-Br 2 S H H H 0 3-NO₂, 5-Br 2 S H H H 1 3-NO₂, 5-Br 2 S H H H2 3-NO₂, 5-Br 2 S H H H 3 3-NO₂, 5-Br 2 S H H H 4 3-NO₂, 5-Br 2 S H H H5 3-NO₂, 5-Br 2 S H H H 6 3-NO₂, 5-Br 2 NH H H H 0 3-NO₂, 4-CH₃ 2 NH H HH 1 3-NO₂, 4-CH₃ 2 NH H H H 2 3-NO₂, 4-CH₃ 2 NH H H H 3 3-NO₂, 4-CH₃ 2NH H H H 4 3-NO₂, 4-CH₃ 2 NH H H H 5 3-NO₂, 4-CH₃ 2 NH H H H 6 3-NO₂,4-CH₃ 2 S H H H 0 3-NO₂, 4-CH₃ 2 S H H H 1 3-NO₂, 4-CH₃ 2 S H H H 23-NO₂, 4-CH₃ 2 S H H H 3 3-NO₂, 4-CH₃ 2 S H H H 4 3-NO₂, 4-CH₃ 2 S H H H5 3-NO₂, 4-CH₃ 2 S H H H 6 3-NO₂, 4-CH₃ 2 O H H H 0 3-NO₂, 4-CH₃ 2 O H HH 1 3-NO₂, 4-CH₃ 2 O H H H 2 3-NO₂, 4-CH₃ 2 O H H H 3 3-NO₂, 4-CH₃ 2 O HH H 4 3-NO₂, 4-CH₃ 2 O H H H 5 3-NO₂, 4-CH₃ 2 O H H H 6 3-NO₂, 4-CH₃ 2NH H H H 0 4-CH₃, 5-NO₂ 2 NH H H H 1 4-CH₃, 5-NO₂ 2 NH H H H 2 4-CH₃,5-NO₂ 2 NH H H H 3 4-CH₃, 5-NO₂ 2 NH H H H 4 4-CH₃, 5-NO₂ 2 NH H H H 54-CH₃, 5-NO₂ 2 NH H H H 6 4-CH₃, 5-NO₂ 2 O H H H 0 4-CH₃, 5-NO₂ 2 O H HH 1 4-CH₃, 5-NO₂ 2 O H H H 2 4-CH₃, 5-NO₂ 2 O H H H 0 3,5-(CF₃)₂ 2 O H HH 1 3,5-(CF₃)₂ 2 O H H H 2 3,5-(CF₃)₂ 2 O H H H 3 3,5-(CF₃)₂ 2 O H H H 43,5-(CF₃)₂ 2 O H H H 5 3,5-(CF₃)₂ 2 O H H H 6 3,5-(CF₃)₂ 2 NH H H H 03,5-(CF₃)₂ 2 NH H H H 1 3,5-(CF₃)₂ 2 NH H H H 2 3,5-(CF₃)₂ 2 NH H H H 33,5-(CF₃)₂ 2 NH H H H 4 3,5-(CF₃)₂ 2 NH H H H 5 3,5-(CF₃)₂ 2 NH H H H 63,5-(CF₃)₂ 2 S H H H 0 3,5-(CF₃)₂ 2 S H H H 1 3,5-(CF₃)₂ 2 S H H H 23,5-(CF₃)₂ 2 S H H H 3 3,5-(CF₃)₂ 2 S H H H 4 3,5-(CF₃)₂ 2 S H H H 53,5-(CF₃)₂ 2 S H H H 6 3,5-(CF₃)₂ 2 O H H H 0 5-CF₃ 2 O H H H 1 5-CF₃ 2O H H H 2 5-CF₃ 2 O H H H 3 5-CF₃ 2 O H H H 4 5-CF₃ 2 O H H H 5 5-CF₃ 2O H H H 6 5-CF₃ 2 S H H H 0 5-CF₃ 2 S H H H 1 5-CF₃ 2 S H H H 2 5-CF₃ 2S H H H 3 5-CF₃ 2 S H H H 4 5-CF₃ 2 S H H H 5 5-CF₃ 2 S H H H 6 5-CF₃ 2NH H H H 0 5-CF₃ 2 NH H H H 1 5-CF₃ 2 NH H H H 2 5-CF₃ 2 NH H H H 35-CF₃ 2 NH H H H 4 5-CF₃ 2 NH H H H 5 5-CF₃ 2 NH H H H 6 5-CF₃ 2 NCH₃ HH H 0 5-CF₃ 2 NCH₃ H H H 1 5-CF₃ 2 NCH₃ H H H 2 5-CF₃ 2 NCH₃ H H H 35-CF₃ 2 NCH₃ H H H 4 5-CF₃ 2 N—CH₂CH₃ H H H 0 5-CF₃ 2 N—CH₂CH₃ H H H 15-CF₃ 2 N—CH₂CH₃ H H H 2 5-CF₃ 2 N—CH₂CH₃ H H H 3 5-CF₃ 2 N—CH₂CH₃ H H H4 5-CF₃ 2 N—(CH₂)₂CH₃ H H H 0 5-CF₃ 2 N—(CH₂)₂CH₃ H H H 1 5-CF₃ 2N—(CH₂)₂CH₃ H H H 2 5-CF₃ 2 N—(CH₂)₂CH₃ H H H 3 5-CF₃ 2 N—(CH₂)₂CH₃ H HH 4 5-CF₃ 2 N—CH(CH₃)₂ H H H 0 5-CF₃ 2 N—CH(CH₃)₂ H H H 1 5-CF₃ 2N—CH(CH₃)₂ H H H 2 5-CF₃ 2 N—CH(CH₃)₂ H H H 3 5-CF₃ 2 N—CH(CH₃)₂ H H H 45-CF₃ 2 O H H H 3 4-CH₃, 5-NO₂ 2 O H H H 4 4-CH₃, 5-NO₂ 2 O H H H 54-CH₃, 5-NO₂ 2 O H H H 6 4-CH₃, 5-NO₂ 2 S H H H 0 4-CH₃, 5-NO₂ 2 S H H H1 4-CH₃, 5-NO₂ 2 S H H H 2 4-CH₃, 5-NO₂ 2 S H H H 3 4-CH₃, 5-NO₂ 2 S H HH 4 4-CH₃, 5-NO₂ 2 S H H H 5 4-CH₃, 5-NO₂ 2 S H H H 6 4-CH₃, 5-NO₂ 3 O HH H 0 H 3 O H H H 1 H 3 O H H H 2 H 3 O H H H 3 H 3 O H H H 4 H 3 O H HH 5 H 3 O H H H 6 H 3 O H H H 0 2-CH₃ 3 O H H H 1 2-CH₃ 3 O H H H 22-CH₃ 3 O H H H 3 2-CH₃ 3 O H H H 4 2-CH₃ 3 O H H H 5 2-CH₃ 3 O H H H 62-CH₃ 3 O H H H 0 6-CH₃ 3 O H H H 1 6-CH₃ 3 O H H H 2 6-CH₃ 3 O H H H 36-CH₃ 3 O H H H 4 6-CH₃ 3 O H H H 5 6-CH₃ 3 O H H H 6 6-CH₃ 3 O H H H 05-Cl 3 O H H H 1 5-Cl 3 O H H H 2 5-Cl 3 O H H H 3 5-Cl 3 O H H H 4 5-Cl3 O H H H 5 5-Cl 3 O H H H 6 5-Cl 3 O H H H 0 2-Cl 3 O H H H 1 2-Cl 3 OH H H 2 2-Cl 3 O H H H 3 2-Cl 3 O H H H 4 2-Cl 3 O H H H 5 2-Cl 3 O H HH 6 2-Cl 3 O H H H 0 2-Br 3 O H H H 1 2-Br 3 O H H H 2 2-Br 3 O H H H 32-Br 3 O H H H 4 2-Br 3 O H H H 5 2-Br 3 O H H H 6 2-Br 3 O H H H 0 2-I,6-CH₃ 3 O H H H 1 2-I, 6-CH₃ 3 O H H H 2 2-I, 6-CH₃ 3 O H H H 3 2-I,6-CH₃ 3 O H H H 4 2-I, 6-CH₃ 3 O H H H 5 2-I, 6-CH₃ 3 O H H H 6 2-I,6-CH₃ 3 NH H H H 0 H 3 NH H H H 1 H 3 NH H H H 2 H 3 NH H H H 3 H 3 NH HH H 4 H 3 NH H H H 5 H 3 NH H H H 6 H 3 NH H H H 0 2-Cl 3 NH H H H 12-Cl 3 NH H H H 2 2-Cl 3 NH H H H 3 2-Cl 3 NH H H H 4 2-Cl 3 NH H H H 52-Cl 3 NH H H H 6 2-Cl 3 NH H H H 0 5-OCH₃ 3 NH H H H 1 5-OCH₃ 3 NH H HH 2 5-OCH₃ 3 NH H H H 3 5-OCH₃ 3 NH H H H 4 5-OCH₃ 3 NH H H H 5 5-OCH₃ 3NH H H H 6 5-OCH₃ 3 NH H H H 0 2,6-(OCH₃)₂ 3 NH H H H 1 2,6-(OCH₃)₂ 3 NHH H H 2 2,6-(OCH₃)₂ 3 NH H H H 3 2,6-(OCH₃)₂ 3 NH H H H 4 2,6-(OCH₃)₂ 3NH H H H 5 2,6-(OCH₃)₂ 3 NH H H H 6 2,6-(OCH₃)₂ 4 S H H H 0 H 4 S H H H1 H 4 S H H H 2 H 4 S H H H 3 H 4 S H H H 4 H 4 S H H H 5 H 4 S H H H 6H 4 NH H H H 0 H 4 NH H H H 1 H 4 NH H H H 2 H 4 NH H H H 3 H 4 NH H H H4 H 4 NH H H H 5 H 4 NH H H H 6 H 4 O H H H 0 H 4 O H H H 1 H 4 O H H H2 H 4 O H H H 3 H 4 O H H H 4 H 4 O H H H 5 H 4 O H H H 6 H 4 S H H H 02,3,5,6-Cl₄ 4 S H H H 1 2,3,5,6-Cl₄ 4 S H H H 2 2,3,5,6-Cl₄ 4 S H H H 32,3,5,6-Cl₄ 4 S H H H 4 2,3,5,6-Cl₄ 4 S H H H 5 2,3,5,6-Cl₄ 4 S H H H 62,3,5,6-Cl₄

[0180] TABLE 31    R¹ =

[0181] TABLE 32    R¹ =

[0182] TABLE 33    R¹ =

[0183] TABLE 34 R¹ =

[0184] In Tables 31 to 34, (R⁸)_(r) is defined as follows: (R⁸)_(r)3-Cl, 5-CF₃ 3-Br, 5-CF₃ 3-F, 5-CF₃ 3, 5-(CF₃)₂ 5-CF₃ 3, 5-Cl₂ 6-Cl 6-CF₃6-Br

[0185] TABLE 35

(R⁸)_(r) R¹³ R¹⁴ R⁵ R⁶ p R⁷ H H H H H 0 H H H H H H 1 H 6-Cl H H H H 0 H6-Cl H H H H 1 H 6-Br H H H H 0 H 6-Br H H H H 1 H 6-F H H H H 0 H 6-F HH H H 1 H 6-I H H H H 0 H 6-I H H H H 1 H 6-CH₃ H H H H 0 H 6-CH₃ H H HH 1 H 6-CF₃ H H H H 0 H 6-CF₃ H H H H 1 H 6-Cl CH₃ H H H 0 H 6-Cl CH₃ HH H 1 H 6-CH₃ CH₃ CH₃ H H 0 H 6-CH₃ CH₃ CH₃ H H 1 H 6-CF₃ CH₃ CH₃ H H 0H 6-CF₃ CH₃ CH₃ H H 1 H 6-Cl CH₃ CH₃ H H 0 H 6-Cl CH₃ CH₃ H H 1 H 6-CH₃CH₃ CH₃ H H 0 H 6-CH₃ CH₃ CH₃ H H 1 H 6-CF₃ CH₃ CH₃ H H 0 H 6-CF₃ CH₃CH₃ H H 1 H

[0186] TABLE 36

(R⁸)_(r) R¹³ R¹⁴ R⁵ R⁶ p R⁷ H H H H H 0 H H H H H H 1 H 5-Cl H H H H 0 H5-Cl H H H H 1 H 5-Br H H H H 0 H 5-Br H H H H 1 H 5-F H H H H 0 H 5-F HH H H 1 H 5-I H H H H 0 H 5-I H H H H 1 H 5-CH₃ H H H H 0 H 5-CH₃ H H HH 1 H 5-CF₃ H H H H 0 H 5-CF₃ H H H H 1 H 5-Cl CH₃ H H H 0 H 5-Cl CH₃ HH H 1 H 5-CH₃ CH₃ CH₃ H H 0 H 5-CH₃ CH₃ CH₃ H H 1 H 5-CF₃ CH₃ CH₃ H H 0H 5-CF₃ CH₃ CH₃ H H 1 H 5-Cl CH₃ CH₃ H H 0 H 5-Cl CH₃ CH₃ H H 1 H 5-CH₃CH₃ CH₃ H H 0 H 5-CH₃ CH₃ CH₃ H H 1 H 5-CF₃ CH₃ CH₃ H H 0 H 5-CF₃ CH₃CH₃ H H 1 H

[0187] TABLE 37

(R⁸)_(r) R¹¹ R¹² s R⁵ R⁶ p R⁷ H H H 1 H H 1 H H H H 2 H H 1 H 5-Cl H H 1H H 1 H 5-Cl H H 2 H H 1 H 5-CF₃ H H 1 H H 1 H 5-CF₃ H H 2 H H 1 H

[0188] TABLE 38

(R⁸)_(r) R¹³ R¹⁴ R⁵ R⁶ p R⁷ H H H H H 1 H H H H H H 2 H 6-Cl H H H H 1 H6-Cl H H H H 2 H 6-Br H H H H 1 H 6-Br H H H H 2 H 6-F H H H H 1 H 6-F HH H H 2 H 6-I H H H H 1 H 6-I H H H H 2 H 6-CH₃ H H H H 1 H 6-CH₃ H H HH 2 H 6-CF₃ H H H H 1 H 6-CF₃ H H H H 2 H

[0189] TABLE 39

(R⁸)_(r) R¹³ R¹⁴ R⁵ R⁶ p R⁷ H H H H H 1 H H H H H H 2 H 5-Cl H H H H 1 H5-Cl H H H H 2 H 5-Br H H H H 1 H 5-Br H H H H 2 H 5-F H H H H 1 H 5-F HH H H 2 H 5-I H H H H 1 H 5-I H H H H 2 H 5-CH₃ H H H H 1 H 5-CH₃ H H HH 2 H 5-CF₃ H H H H 1 H 5-CF₃ H H H H 2 H

[0190] TABLE 40

(R⁸)_(r) R¹¹ R¹² s B R⁵ R⁶ p R⁷ H H H 1 COO H H 1 H H H H 2 COO H H 1 HH H H 1 COO H H 2 H H H H 2 COO H H 2 H 6-CH₃ H H 1 COO H H 1 H 6-CH₃ HH 2 COO H H 1 H 6-CH₃ H H 1 COO H H 2 H 6-CH₃ H H 2 COO H H 2 H

[0191] TABLE 41

Bonding position of heterocyclic ring B (R₈)_(r) R⁵ R⁶ p R⁷ 2 COO H H H2 H 2 COO H H H 3 H 3 COO H H H 2 H 3 COO H H H 3 H 2 O H H H 1 H 2 O HH H 2 H 2 O H H H 3 H 2 S H H H 1 H 2 S H H H 2 H 2 S H H H 3 H 2 NH H HH 1 H 2 NH H H H 2 H 2 NH H H H 3 H 2 NH H H H 1 H 2 NH H H H 2 H 2 NH HH H 3 H

[0192] TABLE 42

(R⁸)_(r) R⁵ R⁶ p R⁷ H H H 0 H H H H 1 H H H H 2 H H H H 3 H

[0193] TABLE 43

(R⁸)_(r) R⁵ R⁶ p R⁷ 3-Br, 5-CF₃ H H 1 H 3-Br, 5-CF₃ H H 2 H 3-Br, 5-CF₃H H 3 H 3-Cl, 5-CF₃ H H 1 H 3-Cl, 5-CF₃ H H 2 H 3-Cl, 5-CF₃ H H 3 H 3-F,5-CF₃ H H 1 H 3-F, 5-CF₃ H H 2 H 3-F, 5-CF₃ H H 3 H 3,5-(CF₃)₂ H H 1 H3,5-(CF₃)₂ H H 2 H 3,5-(CF₃)₂ H H 3 H 5-CF₃ H H 1 H 5-CF₃ H H 2 H 5-CF₃H H 3 H

[0194] TABLE 44

(R⁸)_(r) R⁵ R⁶ p R⁷ C₆H₅ H H 0 H C₆H₅ H H 1 H C₆H₅ H H 2 H C₆H₅ H H 3 HC₆H₄(4-Cl) H H 0 H C₆H₄(4-Cl) H H 1 H C₆H₄(4-Cl) H H 2 H C₆H₄(4-Cl) H H3 H C₆H₄(4-CF₃) H H 0 H C₆H₄(4-CF₃) H H 1 H C₆H₄(4-CF₃) H H 2 HC₆H₄(4-CF₃) H H 3 H C₆H₄(4-OCF₃) H H 0 H C₆H₄(4-OCF₃) H H 1 HC₆H₄(4-OCF₃) H H 2 H C₆H₄(4-OCF₃) H H 3 H C₆H₄(4-Br) H H 0 H C₆H₄(4-Br)H H 1 H C₆H₄(4-Br) H H 2 H C₆H₄(4-Br) H H 3 H

[0195] TABLE 45

(R⁸)_(r) R B R⁵ R⁶ p R⁷ H S S H H 1 H H S S H H 2 H H S O H H 1 H H S OH H 2 H H S NH H H 1 H H S NH H H 2 H H S S H H 2 H H S O H H 2 H 2-CF₃S NH H H 2 H 2-CF₃ S S H H 2 H 2-CF₃ S O H H 2 H 3-CF₃ S NH H H 2 H3-CF₃ S S H H 2 H 3-CF₃ S O H H 2 H 2-OCF₃ S NH H H 2 H 2-OCF₃ S S H H 2H 2-OCF₃ S O H H 2 H 3-OCF₃ S NH H H 2 H 3-OCF₃ S S H H 2 H 3-OCF₃ S O HH 2 H 2-Cl S NH H H 2 H 2-Cl S S H H 2 H 2-Cl S O H H 2 H 3-Cl S NH H H2 H 3-Cl S S H H 2 H 3-Cl S O H H 2 H 3-Cl S NH H H 2 H 2-Br S S H H 2 H2-Br S O H H 2 H 2-Br S NH H H 2 H 3-Br S S H H 2 H 3-Br S O H H 2 H3-Br S NH H H 2 H 3,4-(CH₃)₂ S S H H 2 H 3,4-(CH₃)₂ S O H H 2 H3,4-(CH₃)₂ S NH H H 2 H 3-OCH₃ S S H H 2 H 3-OCH₃ S O H H 2 H 3-OCH₃ SNH H H 2 H 3-OCH₂CH₃ S S H H 2 H 3-OCH₂CH₃ S O H H 2 H 3-OCH₂CH₃ S NH HH 2 H 4-OCH₃ S S H H 2 H 4-OCH₃ S O H H 2 H 4-OCH₃ S NH H H 2 H4-OCH₂CH₃ S S H H 2 H 4-OCH₂CH₃ S O H H 2 H 4-OCH₂CH₃ S NH H H 2 H3-OCH(CH₃)₂ S S H H 2 H 3-OCH(CH₃)₂ S O H H 2 H 3-OCH(CH₃)₂ S NH H H 2 H4-OCH(CH₃)₂ S S H H 2 H 4-OCH(CH₃)₂ S O H H 2 H 4-OCH(CH₃)₂ S NH H H 2 HH NH S H H 1 H H NH S H H 2 H 2-CH₃ NH S H H 1 H 2-CH₃ NH S H H 2 H2-OCH₃ NH S H H 1 H 2-OCH₃ NH S H H 2 H 2-OCF₃ NH S H H 1 H 2-OCF₃ NH SH H 2 H 2-NO₂ NH S H H 1 H 2-NO₂ NH S H H 2 H 2-Cl NH S H H 1 H 2-Cl NHS H H 2 H 2-Br NH S H H 1 H 2-Br NH S H H 2 H 2-CH₃ NH O H H 1 H 2-CH₃NH NH H H 2 H 2-OCH₃ NH O H H 1 H 2-OCH₃ NH NH H H 2 H 2-OCF₃ NH O H H 1H 2-OCF₃ NH NH H H 2 H 2-Cl NH O H H 1 H 2-Cl NH NH H H 2 H 2-Br NH O HH 1 H 2-Br NH NH H H 2 H H O S H H 1 H H O O H H 1 H H O NH H H 1 H H OS H H 2 H H O O H H 2 H H O NH H H 2 H 2-Cl O S H H 2 H 2-Cl O O H H 2 H2-Cl O NH H H 2 H 3-Cl O S H H 2 H 3-Cl O 0 H H 2 H 3-Cl O NH H H 2 H2-CF₃ O S H H 2 H 2-CF₃ O O H H 2 H 2-CF₃ O NH H H 2 H 3-CF₃ O S H H 2 H3-CF₃ O O H H 2 H 3-CF₃ O NH H H 2 H 2-OCF₃ O S H H 2 H 2-OCF₃ O O H H 2H 2-OCF₃ O NH H H 2 H 3-OCF₃ O S H H 2 H 3-OCF₃ O O H H 2 H 3-OCF₃ O NHH H 2 H 2-NO₂ NH O H H 1 H 2-NO₂ NH NH H H 2 H

[0196] TABLE 46

(R⁸)_(r) R⁵ R⁶ p R⁷ H H H 1 H H H H 2 H

[0197] The aldehyde compound of the general formula [VI], which is anintermediate for use in the production of the present compounds, can beproduced, for example, according to the following scheme 1:

[0198] wherein all variables are as defined above.

[0199] The compounds of the general formula [II] or [III], which areintermediate for use in the production of the present compounds, can beproduced, for example, according to the following schemes 2 to 6:

[0200] The compounds of the general formula [VII], which areintermediates for use in the production of the present compounds, can beproduced, for example, according to the following scheme 7:

[0201] The compounds of the general formula [IV] and the alcoholcompounds of the general formula [V], which are intermediates for use inthe production of the present compounds, can be produced, for example,according to the following scheme 8:

[0202] wherein L² is chlorine or bromine, L³ is mesyloxy or tosyloxy,and X is as defined above.

[0203] The compounds of the general formula [VIII] or [IX] wherein R¹ isR¹ ₁ (wherein R¹ ₁ is Q₁ or Q₂ in the definition of R¹), which areintermediates for use in the production of the present compounds, can beobtained from various commercial sources or can be produced, forexample, according to the schemes 9 and 10 depicted below.

[0204] The aldehyde compounds of the general formula: A—CHO (wherein Ais as defined above), which are the starting compounds in the productionof the compounds [VIII] or [IX], can be obtained, for example, by theprocesses disclosed in the following references.

[0205] Furancarbaldehydes:

[0206] Zh. Org. Khim., 11, 1955;

[0207] Tetrahedron., 39, 3881;

[0208] Chem. Pharm. Bull., 28, 2846

[0209] Thiophenecarbaldehydes:

[0210] Tetrahedron., 32, 1403;

[0211] J. Org. Chem., 41, 2835;

[0212] Zh. Obshch. Khim., 34, 4010;

[0213] Bull. Soc. Chim. France., 479 (1963)

[0214] Pyrrolecarbaldehydes:

[0215] Beilstein., 21, 1279

[0216] Isothiazolecarbaldehydes:

[0217] J. Medicin. Chem., 13, 1208;

[0218] J. Chem. Soc., 446 (1964)

[0219] Pyrazolecarboaldehydes:

[0220] Chem. Ber., 97, 3407;

[0221] J. Chem. Soc., 3314 (1957)

[0222] Imidazolecarbaldehydes:

[0223] J. Pharm. Soc. Japan., 60, 184;

[0224] J. Amer. Chem. Soc., 71, 2444

[0225] Thiazolecarbaldehydes:

[0226] JP-A 59-206370/1984

[0227] Chem. Ab., 62, 7764d;

[0228] Chem. Ber., 101, 3872;

[0229] JP-A 59-206370/1984

[0230] Thiadiazolecarbaldehydes:

[0231] U.S. Pat. No. 1,113,705

[0232] wherein all the variables are each as defined above.

[0233] (R¹—OH when p is 1, and R⁶ and R⁷ are both hydrogen)

[0234] wherein all the variables are each as defined above.

[0235] The compounds of the general formula: A—L′ (wherein L′ is halogen(e.g., chlorine, bromine, iodine)) included in the compounds [XI], whichare intermediates for use in the production of the present compounds,can be obtained from various commercial sources or can be produced, forexample, according to the following scheme 11:

[0236] wherein A and L′ are each as defined above.

[0237] The compounds [X], [XII] or [XIII], which are intermediates foruse in the production of the present compounds, can be produced, forexample, according to the following schemes 12 and 13:

[0238] wherein all the variables are each as defined above.

[0239] *) J.Amer.Chem.Soc., 33, 440 (1905)

[0240] wherein M_(s) is mesyl; T_(s) is tosyl; R¹⁶ is a protecting groupfor alcohols (e.g., benzoyl); R¹⁷ is protected formyl (e.g., acetal); L¹is hydroxy or L; and R², R³, R⁷, R¹⁰, R¹¹, R¹⁴, X, L, p and t are eachas defined above.

[0241] (R⁵, R⁶ and R⁷ are all hydrogen in [IV])

[0242] wherein all the variables are each as defined above.

[0243] The present compounds are satisfactorily effective for thecontrol of various noxious insects, mites-and ticks, examples of whichare as follows:

[0244] Hemiptera:

[0245] Delphacidae such as Laodelphax striatellus, Nilaparvata lugensand Sogatella furcifera, Deltocephalidae such as Nephotettix cincticepsand Nephotettix virescens, Aphididae, Pentatomidae, Aleyrodidae,Coccidae, Tingidae, Psyllidae, etc.

[0246] Lepidoptera:

[0247] Pyralidae such as Chilo suppressalis, Cnaphalocrocis medinalis,Ostrinia nubilalis, Parapediasia teterrella, Notarcha dercogata andPlodia interpunctella, Noctuidae such as Spodoptera litura, Spodopteraexigua, Spodoptera littoralis, Pseudaletia separata, Mamestra brassicae,Agrotis ipsilon, Trichoplusia spp., Heliothisspp., Helicoverpa spp. andEarias spp., Pieridae such as Pieris rapae crucivora, Tortricidae suchas Adoxophyes spp., Grapholita molesta and Cydia pomonella, Carposinidaesuch as Carposina niponensis, Lyonetiidae such as Lyonetia spp.,Lymantriidae such as Lymantria spp. and Euproctis spp., Yponomeutidaesuch as Plutella xylostella, Gelechiidae such as Pectinophoragossypiella, Arctiidae such as Hyphantria cunea, Tineidue such as Tineatranslucens and Tineola bisselliella, etc.

[0248] Diptera:

[0249] Culex such as Culex pipiens pallens and Cules tritaeniorhynchus,Aedes such as Aedes albopictus and Aedes aegypti, Anopheles such asAnophelinae sinensis, Chironomidae, Muscidae such as Musca domestica andMuscina stabulans, Calliphoridae, Sarcophagidae, Fannia canicularis,Anthomyiidae such as Delia Platura and Delia antigua, Trypetidae,Drosophilidae, Psychodidae, Tabanidae, Simuliidae, Stomoxyinae, etc.

[0250] Coleoptera:

[0251] Diabrotica such as Diabrotica virgifera and Diabroticaundecimpunctata, Scarabaeidae such as Anomala cuprea and Anomalarufocuprea, Curculionidae such as Lissorphoptrus oryzophilus, Hyperapastica, and Calosobruchys chinensis, Tenebrionidae such as Tenebriomolitor and Tribolium castaneum, Chrysomelidae such as Phyllotretastriolata and Aulacophora femoralis, Anobiidae, Epilachna spp. such asHenosepilachna vigintioctopunctata, Lyctidae, Bostrychidae,Cerambycidae, Paederus fuscipes, etc.

[0252] Dictyoptera:

[0253]Blattella germanica, Periplaneta fuligitiosa, Peroplanetaamericans, Periplaneta brunnea, Blatta orientalis, etc.

[0254] Thysanoptera:

[0255]Thrips palmi, Thrips hawaiiensis, etc.

[0256] Hymenoptera:

[0257] Formicidae, Vespidae, Bethylidae, Tenthredinidae such as Athaliarosae japonensis, etc.

[0258] Orthoptera:

[0259] Gryllotalpidae, Acrididae, etc.

[0260] Siphonaptera:

[0261]Purex irritans, etc.

[0262] Anoplura:

[0263]Pediculus humanus capitis, Phthirus pubis, etc.

[0264] Isoptera (termites):

[0265]Reticulitermes speratus, Coptotermes formosanus, etc.

[0266] Acarina:

[0267] plant patasitic Tetranychidae such as Tetranychus uriticae,Panonychus citri, Tetranychus cinnabarinus and Panonychiis ulmi, animalparasitic Ixodidae such as Boophilus microphus, house dust mites, etc.

[0268] The present compounds are also effective for the control ofvarious noxious insects, mites and ticks having resistance toconventional insecticides and acaricides.

[0269] When the present compound is used as an active ingredient ofinsecticidal/acaricidal agents, it may be used as such without anyaddition of other ingredients. The present compound is, however, usuallyformulated into a dosage form such as oil sprays, emulsifiableconcentrates, wettable powders, flowables, granules, dusts, aerosols,fumigants (foggings) and poison baits. These formulations are usuallyprepared by mixing the present compound with a solid carrier, a liquidcarrier, a gaseous carrier or a bait, and if necessary, adding asurfactant and other auxiliaries used for formulation.

[0270] Each of the formulations usually contains the present compound asan active ingredient in an amount of 0.01% to 95% by weight.

[0271] Examples of the solid carrier to be used for the formulation arefine powder or granules of clay materials such as kaolin clay,diatomaceous earth, synthetic hydrated silicon oxide, bentonite,Fubasami clay and acid clay; various kinds of talc, ceramics, otherinorganic minerals such as sericite, quartz, sulfur, active carbon,calcium carbonate and hydrated silica; and chemical fertilizers such asammonium sulfate, ammonium phosphate, ammonium nitrate, urea andammonium chloride.

[0272] Examples of the liquid carrier are water; alcohols such asmethanol and ethanol; ketones such as acetone and methyl ethyl ketone;aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene andmethylnaphthalene; aliphatic hydrocarbons such as hexane, cyclohexane,kerosine and gas oil; esters such as ethyl acetate and butyl acetate;nitrites such as acetonitrile and isobutyronitrile; ethers such asdiisopropyl ether and dioxane; acid amides such as N,N-dimethylformamideand N,N-dimethylacetamide; halogenated hydrocarbons such asdichloromethane, trichloroethane and carbon tetrachloride; dimethylsulfoxide; and vegetable oils such as soybean oil and cottonseed oil.

[0273] Examples of the gaseous carrier or propellant are flon gas,butane gas, LPG (liquefied petroleum gas), dimethyl ether and carbondioxide.

[0274] Examples of the surfactant are alkyl sulfates, alkyl sulfonates,alkyl arylsulfonates, alkyl aryl ethers and their polyoxyethylenederivatives, polyethylene glycol ethers, polyhydric alcohol esters andsugar alcohol derivatives.

[0275] Examples of the auxiliaries used for formulation, such as fixingagents or dispersing agents, are casein, gelatin, polysaccharides suchas starch, gum arabic, cellulose derivatives and alginic acid, ligninderivatives, bentonite, sugars, and synthetic water-soluble polymerssuch as polyvinyl alcohol, polyvinyl pyrrolidone and polyacrylic acid.

[0276] Examples of the stabilizer are PAP (isopropyl-acid phosphate),BHT (2,6-di-tert-butyl-4-methylphenol), BHA (mixtures of2-t-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetableoils, mineral oils, surfactants, fatty acids and their esters.

[0277] Examples of the base material to be used in the poison baits arebait materials such as grain powder, vegetable oils, sugars andcrystalline cellulose; antioxidants such as dibutylhydroxytoluene andnordihydroguaiaretic acid; preservatives such as dehydroacetic acid;substances for preventing erroneous eating, such as red pepper powder,attractant flavors such as cheese flavor or onion flavor.

[0278] The formulation thus obtained is used as such or after dilutedwith water. The formulation may also be used in combination with otherinsecticides, nematocides, acaricides, bactericides, fungicides,herbicides, plant growth regulators, synergists, fertilizers, soilconditioners and/or animal feed under non-mixing conditions orpre-mixing conditions.

[0279] Examples of the insecticide, acaricide and/or nematocide whichcan be used are organophosphorus compounds such as Fenitrothion[(O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate], Fenthion[O,O-dimethyl O-(3-methyl-4-methylthio)phenyl)phophorothioate], Diazinon[O,O-diethyl-O-2-isopropyl-6-methylpyrimidin-4-ylphosphorothioate],Chlorpyriphos [O,O-diethyl-O-3,5,6-trichloro-2-pyridylphosphorothioate],Acephate [O,S-dimethylacetylphosphoramidothioate], Methidachion[S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethylO,O-dimethylphosphorodithioate], Disulfoton [O,O-diethylS-2-ethylthioethylphosphorothioate], DDVP[2,2-dichlorovinyldimethylphosphate], Sulprofos [O-ethylO-4-(methylthio)phenyl S-propyl phosphorodithioate], Cyanophos[O-4-cyanophenyl O,O-dimethylphosphorothioate], Dioxabenzofos[2-methoxy-4H-1,3,2-benzodioxaphosphinin-2-sulfide], Dimethoate[O,O-dimethyl-S-(N-methyl-carbamoylmethyl)dithiophosphate], Phenthoate[ethyl 2-dimethoxyphosphinothioylthio-(phenyl)acetate], Malathion[diethyl(dimethoxyphosphinothioylthio)succinate], Trichlorfon [dimethyl2,2,2-trichloro-1-hydroxyethylphosphonate], Azinphos-methyl[S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-ylmethyl-0,0-dimethylphosphorodithioate],Monocrotophos [dimethyl (E)-1-methyl-2-(methylcarbamoyl)vinylphosphate],Ethion [O,O,O′,O′-tetraethyl S,S′-methylenebis(phosphorodithioate)] andProfenfos [O-4-bromo-2-chlorophenyl O-ethyl S-propylphosphorothioate];carbamate compounds such as BPMC [2-sec-butylphenylmethylcarbamate],Benfuracarb [ethylN-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate],Propoxur [2-isopropoxyphenyl N-methylcarbamate], Carbosulfan[2,3-dihydro-2,2-dimethyl-7-benzo[b]-furanylN-dibutylaminothio-N-methylcarbamate], Carbaril[1-naphthyl-N-methylcarbamate], Methomyl[S-methyl-N-[(methylcarbamoyl)oxy]thioacetoimidate], Ethiofencarb[2-(ethylthiomethyl )phenylmethylcarbamate], Aldicarb[2-methyl-2-(methylthio)propanaldehyde O-methylcarbamoyloxime], Oxamyl[N,N-dimethyl-2-methylcarbamoyloxyimino-2-(methylthio)acetamide],Alanylcarb [ethyl(Z)—N-benzyl-N-{[methyl(1-methyl-thioethylideneaminooxycarbonyl)amino]thio}-β-alanylate],Fenothiocarb [S-(4-phenoxy-butyl)-N,N-dimethylthiocarbamate] andThiodicarb[3,7,9,13-tetramethyl-5,11-dioxa-2,8,14-trithia-4,7,9,12-tetraazapentadeca-3,12-dien-6,10-dione];pyrethroid compounds such as Etofenprox[2-(4-ethoxyphenyl)-2-methylpropyl-3-phenoxybenzylether], Fenvalerate[(RS)-α-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate],Esfenvalerate [(S)-α-cyano-3-phenoxybenzyl(S)-2-(4-chlorophenyl)-3-methylbutyrate], Fenpropathrin[(RS)-α-cyano-3-phenoxybenzyl2,2,3,3-tetramethylcyclopropanecarboxylate], Cypermethrin[(RS)-α-cyano-3-phenoxybenzyl(1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate],Permethrin [3-phenoxybenzyl(1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate],Cyhalothrin [(RS)-α-cyano-3-phenoxybenzyl(Z)-(1RS,3RS)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate],Deltamethrin [(S)-α-cyano-m-phenoxybenzyl(1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate],Cycloprothrin [(RS)-α-cyano-3-phenoxybenzyl(RS)-2,2-dichloro-1-(4-ethoxyphenyl)cyclopropanecarboxylate],Fluvalinate [α-cyano-3-phenoxybenzylN-(2-chloro-α,α,α-trifluoro-p-tolyl)-D-valinate], Bifenthrin[2-methylbiphenyl-3-ylmethyl)(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoropropen-1-yl)-2,2-dimethylcyclopropanecarboxylate],Acrinathrin [cyano-(3-phenoxyphenyl)methyl [1R-{1α(S*),3α((Z)}]-2,2-dimethyl-3-[3-oxo-3-(2,2,2-trifluoro-1-(trifluoromethyl)-ethoxy-1-propenyl]cyclopropanecarboxylate],2-methyl-2-(4-bromodifluoromethoxyphenyl)propyl (3-phenoxybenzyl) ether,Traromethrin [(S)-α-cyano-3-phenoxylbenzyl (1R,3R)-3-[(1′RS)(1′,1′,2′,2′-tetrabromoethyl)]-2,2-dimethylcyclopropanecarboxylate]and Silafluofen [4-ethoxylphenyl[3-(4fluoro-3-phenoxyphenyl)propyl]dimethylsilane]; thiadiazinederivatives such as Buprofezin[2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazin-4-one];nitroimidazolidine derivatives such as Imidacloprid[1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylidenamine];Nereistoxin derivatives such as Cartap[S,S′-(2-dimethylaminotrimethylene)bisthiocarbamate], Thiocyclam[N,N-di-methyl-1,2,3-trithian-5-ylamine] and Bensultap[S,S′-2-dimethylaminotrimethylene di-(benzenethiosulfonate)];N-cyanoamidine derivatives such as acetamiprid[N-cyano-N′-methyl-N′-(6-chloro-3-pyridylmethyl)acetamidine];chlorinated hydrocarbons such as Endosulfan[6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepinoxide],γ-BHC [1,2,3,4,5,6-hexachlorocyclohexane] and Kelthane[1,1-bis(chlorophenyl)-2,2,2-trichloroethanol]; benzoylphenylureacompounds such as Chlorfluazuron[1-(3,5-dichloro-4-(3-chloro-5-trifluoromethylpyridin-2-yloxy)phenyl)-3-(2,6-difluorobenzoyl)urea],Teflubenzuron[1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea] andFulphenoxron[1-(4-(2-chloro-4-trifluoromethylphenoxy)-2-fluorophenyl)-3-(2,6-difluorobenzoyl)urea];formamidine derivatives such as Amitraz[N,N′-[(methylimino)dimethylidine]-di-2,4-xylidine] and Chlordimeform[N′-(4-chloro-2-methylphenyl)-N,N-dimethylmethanimidamide]; thioureaderivatives such as Diafenthiuron[N-(2,6-diisopropyl-4-phenoxyphenyl)-N′-tert-butylcarbodiimide];Fipronyl [5-amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4-trifluoromethylsulfinylpyrazole-3-carbonitrite],Tebfenozide[N-tert-butyl-N′-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide],4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethylpyrrole-3-carbonitrile, Chlorfenapyl[4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-S-trifluoromethylpyrole-3-carbonitril],Bromopropylate [isopropyl 4,4′-dibromobenzylate], Tetradifon[4-chlorophenyl-2,4,5-trichlorophenyl sulfone], Quinomethionate[S,S-6-methylquinoxaline-2,3-diyldithiocarbonate], Propargite[2-(4-tert-butylphenoxy)cyclohexyl prop-2-yl sulfite], Fenbutatin oxide[bis[tris(2-methyl-2-phenylpropyl)tin)oxide], Hexythiazox[(4RS,5RS)-5-(4-chlorophenyl)-N-chlorohexyl-4-methyl-2-oxo-1,3-thiazolidine-3-carboxamide],Chlofentezine [3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine], Pyridaben[2-tert-butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2H)-one],Fenpyroximate[tert-butyl-(E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)methyleneaminooxymethyl]benzoate], Tebfenpyrad[N-4-tert-butylbenzyl)-4-chloro-3-ethyl-1-methyl-5-pyrazol carboxamide],polynactin complexes including tetranactin, dinactin and trinactin;Milbemectin, Avermectin, Ivermectin, Azadilactin [AZAD], Pyrimidifen[5-chloro-N-[2-{4-(2-ethoxyethyl)-2,3-dimethylphenoxy}ethyl]-6-ethylpyrimidin-4-amine]and Pimetrozine[2,3,4,5-tetra-hydro-3-oxo-4-[(pyridin-3-yl)-methyleneamino]-6-methyl-1,2,4-triazine].

[0280] When the present compound is used as an active ingredient ofinsecticidal/-acaricidal agents for agriculture, the application amountthereof is usually in the range of 0.1 to 100 g per 10 ares. In the caseof emulsifiable concentrates, wettable powders and flowableconcentrates, which are used after diluted with water, the applicationconcentration thereof is usually in the range of 0.1 to 500 ppm. In thecase of granules and dusts, they are applied as such without anydilution. When the present compound is used as an active ingredient ofinsecticidal/acaricidal agents for epidemic prevention, it is formulatedinto a dosage form such as emulsifiable concentrates, wettable powdersand flowable concentrates, which are applied after diluted with water toa typical concentration of 0.1 to 500 ppm; or it is formulated into adosage form such as oil sprays, aerosols, fumigants and poisonous baits,which are applied as such without any dilution.

[0281] The application amount and application concentration may varydepending upon various conditions such as formulation type, applicationtime, place and method, kind of noxious insects, mites and ticks, anddegree of damage, and they can be increased or decreased withoutlimitation to the above range.

[0282] The present invention will be further illustrated by thefollowing production examples, formulation examples and test examples,which are not to be construed to limit the scope thereof.

[0283] The following are production examples for the present compoundsaccording to various production processes.

PRODUCTION EXAMPLE 1 Production of Compound (10) by Production Process E

[0284] To a solution of 0.44 g of4-(3,3-dichloro-2-propenyloxy)-2,6-dichlorophenol, 0.20 g of2-(2-hydroxyethyl)thiophene and 0.40 g of triphenylphosphine dissolvedin 10 ml of tetrahydrofuran was added dropwise a solution of 0.31 g ofdiisopropyl azodicarboxylate dissolved in 5 ml of tetrahydrofuran, whilestirring at room temperature. After stirring at room temperature for 12hours, the reaction mixture was concentrated, to which 20 ml of diethylether was added, and the precipitate was filtered. The filtrate wasconcentrated, and the residue was subjected to silica gelchromatography, which afforded 0.38 g of3,5-dichloro-4-(2-(2-thienyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene(62% yield), n_(D) ^(25.6) 1.5919.

PRODUCTION EXAMPLE 2 Production of Compound (1) by Production Process D

[0285] To a mixture of 0.40 g of2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 0.21 g of potassiumcarbonate and 20 ml of N,N-dimethylformamide was added dropwise asolution of 0.25 g of 6-chloro-3-(chloromethyl)pyridine dissolved in 5ml of N,N-dimethylformamide, while stirring at room temperature. Afterstirring at room temperature for 7 hours, the reaction mixture waspoured into ice-water, and extracted twice with 50 ml of diethyl ether.The combined ether layer was washed with water, dried with anhydrousmagnesium sulfate, and concentrated to obtain a crude product. The crudeproduct was subjected to silica gel chromatography, which afforded 0.44g of3,5-dichloro-4-(6-chloro-3-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene(77% yield), m.p. 93.3° C.

PRODUCTION EXAMPLE 3 Production of Compound (9) by Production Process E

[0286] To a solution of 0.43 g of4-(3,3-dichloro-2-propenyloxy)-2,6-dichlorophenol, 0.16 g of4-(hydroxymethyl)pyridine and 0.39 g of triphenylphosphine dissolved in10 ml of tetrahydrofuran was added dropwise a solution of 0.30 g ofdiisopropyl azodicarboxylate dissolved in 5 ml of tetrahydrofuran, whilestirring at room temperature. After stirring at room temperature for 12hours, the reaction mixture was concentrated, to which 20 ml of diethylether was added, and the precipitate was filtered. The filtrate wasconcentrated, and the residue was subjected to silica gelchromatography, which afforded 0.29 g of3,5-dichloro-4-(4-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene(51% yield), m.p. 74.0° C.

PRODUCTION EXAMPLE 4 Production of Compound (25) by Production Process H

[0287] A reaction vessel was charged with 0.20 g of3,5-dichloro-4-(3-bromopropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene,0.08 g of thiophene-2-carboxylic acid, 0.08 g of potassium carbonate and10 ml of N,N-dimethylformamide. After stirring at room temperature for12 hours, the reaction mixture was poured into water, and extractedtwice with 30 ml of diethyl ether. The combined ether layer was washedwith water, dried with anhydrous magnesium sulfate, and concentrated toobtain a crude product. The crude product was subjected to silica gelchromatography, which afforded 0.18 g of3,5-dichloro-4-(3-(thiophene-2-carboxylate)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene(81% yield), n_(D) ^(24.0) 1.5814.

PRODUCTION EXAMPLE 5 Production of Compound (29) by Production Process E

[0288] To a mixture of 0.4 g of2-[2-(4-chlorophenyl)-1,3-dioxolan-4-yl]ethanol, 0.46 g oftriphenylphosphine and 6 ml of tetrahydrofuran was added dropwise 0.35ml of diisopropyl azodicarboxylate, while stirring at room temperature.After further stirring for 15 minutes, a solution of 0.5 g of4-(3,3-dichloro-2-propenyloxy)-2,6-dichlorophenol in 2 ml oftetrahydrofuran was added. After stirring continued at room temperaturefor 3 hours, the reaction mixture was concentrated, and the residue wassubjected to silica gel chromatography, which afforded 0.3 g of3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-[2-[2-(4-chlorophenyl)-1,3-dioxolan-4-yl]ethoxy]benzene(35% yield), m.p. 84.]° C.

PRODUCTION EXAMPLE 6 Production of Compound (45) by Production Process E

[0289] To a solution of 0.33 g of2-(3-hydroxypropyloxy)-5-trifluoromethylpyridine, 0.40 g of2-chloro-6-methyl-4-(3,3-dichloro-2-propenyloxy)phenol and 0.41 g oftriphenylphosphine dissolved in 30 ml of dichloromethane was addeddropwise a solution of 0.32 g of diisopropyl azodicarboxylate dissolvedin 3 ml of dichloromethane, while stirring at room temperature. Afterstirring at room temperature for 24 hours, the reaction mixture wasconcentrated to obtain a residue. The residue was subjected to silicagel chromatography, which afforded 0.56 g of3-chloro-5-methyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]-1-(3,3-dichloro-2-propenyloxy)benzene (92% yield), n_(D) ^(23.6)1.5294.

PRODUCTION EXAMPLE 7 Production of Compound (46) by Production Process E

[0290] To a solution of 0.26 g of2-(4-hydroxybutyloxy)-5-trifluoromethylpyridine, 0.3 g of2-chloro-6-methyl-4-(3,3-dichloro-2-propenyloxy)phenol and 0.31 g oftriphenylphosphine dissolved in 30 ml of dichloromethane was addeddropwise a solution of 0.24 g of diisopropyl azodicarboxylate dissolvedin 5 ml of dichloromethane, while stirring at room temperature. Afterstirring at room temperature for 24 hours, the reaction mixture wasconcentrated to obtain a residue. The residue was subjected to silicagel chromatography, which afforded 0.50 g of3-chloro-5-methyl-4-[4-(5-trifluoromethyl-2-pyridyloxy)butyloxy]-1-(3,3-dichloro-2-propenyloxy)benzene(89% yield), n_(D) ^(23.0) 1.5275.

PRODUCTION EXAMPLE 8 Production of Compound (47) by Production Process A

[0291] In 10 ml of N,N-dimethylformamide were dissolved 0.7 g of3-ethyl-5-methyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]phenoland 0.27 g of potassium carbonate, to which a solution of 0.34 g of1,1,3-trichloropropene dissolved in 5 ml of N,N-dimethylformamide wasadded dropwise, while stirring at room temperature. After stirring atroom temperature for 12 hours, the reaction mixture was poured intoice-water, and extracted twice with 100 ml of diethyl ether. Thecombined diethyl ether was washed with water, dried with anhydrousmagnesium sulfate, and concentrated to obtain a crude product. The crudeproduce was subjected to silica gel chromatography, which afforded 0.6 gof3-ethyl-5-methyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]-1-(3,3-di-chloro-2-propenyloxy)benzene(65% yield), n_(D) ^(23.0) 1.5188.

PRODUCTION EXAMPLE 9 Production of Compound (48) by Production Process A

[0292] In 10 ml of N,N-dimethylformamide were dissolved 0.6 g of3-ethyl-5-methyl-4-[4-(5-trifluoromethyl-2-pyridyloxy)butyloxy]phenoland 0.23 g of potassium carbonate, to which a solution of 0.28 g of1,1,3-trichloropropene dissolved in 5 ml of N,N-dimethylformamide wasadded dropwise, while stirring at room temperature. After stirring atroom temperature for 12 hours, the reaction mixture was poured intoice-water, and extracted twice with 100 ml of diethyl ether. Thecombined diethyl ether was washed with water, dried with anhydrousmagnesium sulfate, and concentrated to obtain a crude product. The crudeproduce was subjected to silica gel chromatography, which afforded 0.50g of3-ethyl-5-methyl-4-[4-(5-trifluoromethyl-2-pyridyloxy)butyloxy]-1-(3,3-di-chloro-2-propenyloxy)benzene(64% yield), n_(D) ^(23.0) 1.5170.

PRODUCTION EXAMPLE 10 Production of Compound (50) by Production ProcessA

[0293] In 10 ml of N,N-dimethylformamide were dissolved 0.45 g of3,5-diethyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]phenol and0.17 g of potassium carbonate, to which a solution of 0.18 g of1,1,3-trichloropropene dissolved in 5 ml of N,N-dimethylformamide wasadded dropwise, while stirring at room temperature. After stirring atroom temperature for 12 hours, the reaction mixture was poured intoice-water, and extracted twice with 100 ml of diethyl ether. Thecombined diethyl ether was washed with water, dried with anhydrousmagnesium sulfate, and concentrated to obtain a crude product. The crudeproduce was subjected to silica gel chromatography, which afforded 0.35g of3,5-diethyl-4-[3-(5-trifluoromethyl-2-pyridyloxy)propyloxy]-1-(3,3-dichloro-2-propenyloxy)benzene(60% yield), n_(D) ^(20.0) 1.5192.

PRODUCTION EXAMPLE 11 Production of Compound (49) by production processH

[0294] A mixture of 1.0 g of1-(3-bromopropyloxy)-2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)benzeneand 4.0 g of 2-amino-5-(trifluoromethyl)pyridine was stirred at 90° C.for 3 hours. The reaction mixture was cooled to room temperature, andsubjected to silica gel chromatography, which afforded 0.14 g of3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-(3-(5-(trifluoromethyl)-2-pyridylamino)propyloxy)benzene(12% yield), n_(D) ^(25.0) 1.5525.

PRODUCTION EXAMPLE 12 Production of Compound (36) by Production ProcessA

[0295] A mixture of 0.5 g of3,5-dichloro-4-[3-(5-trifluoromethylpyridin-2-yloxy)-propyloxy]phenol,0.25 g of 1,1,3-trichloropropene, 0.2 g of potassium carbonate and 3 mlof N,N-dimethylformamide was stirred at room temperature overnight. Thereaction mixture was subjected to silica gel chromatography, whichafforded 0.3 g of3,5-di-chloro-1-(3,3-dichloro-2-propenyloxy)-4-[3-(5-trifluoromethylpyridin-2-yloxy)propyl-oxy]benzene(47% yield), n_(D) ^(20.5) 1.5377.

PRODUCTION EXAMPLE 13 Production of Compound (36) by Production ProcessF

[0296] First,2-(3-methanesulfonyloxypropyloxy)-5-trifluoromethylpyridine was preparedas follows.

[0297] A mixture of 12.6 g of 1,3-propanediol and 100 ml ofN,N-dimethylformamide was stirred under a nitrogen stream, to which 3.30g of an oily mixture containing 60% sodium hydride was added in smallportions at room temperature over 30 minutes, After further stirringcontinued at room temperature for 1 hour, 20 ml of a DMF solution of10.0 g of 2-chloro-5-trifluoromethylpyridine was added dropwise over 40minutes. After further stirring continued under a nitrogen stream atroom temperature overnight, 100 ml of about 2 N diluted hydrochloricacid was added over 15 minutes to stop the reaction. The reactionmixture was extracted twice with toluene at a total volume of 500 ml.The combined toluene layer was successively washed with dilutedhydrochloric acid and aqueous sodium bicarbonate solution, dried withmagnesium sulfate, and concentrated to obtain an oily product. The oilyproduct was dissolved in 300 ml of hexane by heating, followed byrecrystallization, which afforded 5.3 g of2-(3-hydroxypropyloxy)-5-trifluoromethylpyridine as almost pure crystals(44% yield), m.p. 46.6° C.

[0298] A mixture of 4.0 g of2-(3-hydroxypropyloxy)-5-trifluoromethylpyridine, 3.4 ml oftriethylamine and 25 ml of toluene was vigorously stirred under anitrogen stream, while cooling in chilled water bath to 5° C. Then, 1.63g of methanesulfonyl chloride was added dropwise to this mixture at sucha rate that the reaction temperature did not exceed 10° C., and thechilled water bath was removed. After further stirring continued at roomtemperature for 1.5 hours, 250 ml of water was added thereto, and themixture was vigorously stirred for further 30 minutes, followed by phaseseparation. The toluene layer was washed once with water, dried withmagnesium sulfate, and concentrated, which afforded 5 g of2-(3-methanesulfonyloxypropyloxy)-5-trifluoromethylpyridine as an oilyproduct (92% yield).

[0299]¹H-NMR δ (ppm) [CDCl₃, TMS] 8.39 (1H, br, s), 7.75 (1H, dd), 6.80(1H, d), 4.0-5.0 (4H), 3.00 (3H, s), 2.30 (2H, quint.)

[0300] A mixture of 5 g of2-(3-methanesulfonyloxypropyloxy)-5-trifluoromethylpyridine, 5 g of4-(3,3-dichloro-2-propenyloxy)-2,6-dichlorophenol, 2.64 g of potassiumcarbonate and 300 ml of N,N-dimethylformamide was vigorously stirred atroom temperature for 4 days. Then, 300 ml of 2 N hydrochloric acid wasadded to this mixture, and extracted twice with toluene at a totalvolume of 300 ml. The combined toluene layer was successively washedwith 2 N hydrochloric acid and aqueous sodium bicarbonate solution,dried with magnesium sulfate, and concentrated to obtain about 8 g of anoily product. The oily product was subjected to silica gelchromatography, which afforded 6.0 g of3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-[3-(5-trifluoromethyl-pyridin-2-yloxy)propyloxy]benzene(70% yield).

[0301] The following are specific examples of the present compound underthe corresponding compound numbers with their physical properties, ifmeasured.

[0302] (1)3,5-Dichloro-4-(6-chloro-3-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 93.3° C.

[0303] (2)3,5-Dichloro-4-(2,6-dichloro-3-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 73.3° C.

[0304] (3)3,5-Dichloro-4(2-(1-pyrazolynyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 59.8° C.

[0305] (4)3,5-Dichloro-4-(2-(1-pyrazolynyl)ethoxy)-1-(3,3-dibromo-2-propenyloxy)benzenem.p. 55.3° C.

[0306] (5)3,5-Dichloro-4-(2-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 48.2° C.

[0307] (6)3,5-Dichloro-4-(2-thienylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 44.6° C.

[0308] (7)3,5-Dichloro-4-(2-furanylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 46.0° C.

[0309] (8)3,5-Dichloro-4-(3-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 105.9° C.

[0310] (9)3,5-Dichloro-4-(4-pyridylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 74.0° C.

[0311] (10)3,5-Dichloro4-(2-(2-thienyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(25.6) 1.5919

[0312] (11)3,5-Dichloro4-(2-(3-methylthiazol-2-yl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 30.4° C.

[0313] (12)3,5-Dichloro-4-(2,4,5-trichloroimidazolynylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 67.5° C.

[0314] (13)3,5-Dichloro-4-(3,5-dimethyl-4-isoxazolynylmethyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 127.4° C.

[0315] (14)3,5-Dichloro-4-(2-(3-thienyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(24.0) 1.5916

[0316] (15)3,5-Dichloro-4-(3-(4-pyridyl)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(24.1) 1.5566

[0317] (16) 3,5-Dichl oro-4-( (2-(1,4-benzodioxanyl))methoxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D) ^(24.6)1.5799

[0318] (17)3,5-Dichloro-4-((2-(5-formyl)furanyl)methoxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 91.5° C.

[0319] (18)3,5-Dichloro-4-((3-(6-methylpyridyl))methoxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 86.7° C.

[0320] (19)3,5-Dichloro-4-(2-(4-pyridylthio)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 74.7° C.

[0321] (20)3,5-Dichloro-4-(3-(3-pyridyl)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 48.3° C.

[0322] (21) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propylnicotinate n_(D) ^(22.5) 1.5674

[0323] (22) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propylisonicotinate n_(D) ^(25.5) 1.5667

[0324] (23) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propylquinolinate n_(D) ^(25.5) 1.6002

[0325] (24) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl2-furanate n_(D) ^(24.0) 1.5589

[0326] (25) 3-(2,6-Dichloro-4-(3,3-dichoro-2-propenyloxy)phenoxy)propyl2-thiophenate n_(D) ^(24.1) 1.5814

[0327] (26) 3-(2;6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl3-thiophenate n_(D) ^(24.0) 1.5788

[0328] (27) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propylpicolinate n_(D) ^(24.0) 1.5737

[0329] (28) 3-(2,6-Dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)propyl3-quinolinate m.p. 92.3° C.

[0330] (29)3,5-Dichloro-4-(2-(2-((2-(4-chlorophenyl)-1,3-dioxanyl)))ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 84.1° C.

[0331] (30)3,5-Dichloro-4-(3-(2-pyridylthio)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(22.5) 1.5982

[0332] (31)3,5-Dichloro-4-(2-(6-ethoxy-2-benzothiezolyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 80.6° C.

[0333] (32)3,5-Dichloro-4-(2-(2-benzoxazolyl)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 61.2° C.

[0334] (33)3,5-Dichloro-4-(2-methyl-2-(2-(6-chloro)pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(22.5) 1.5742

[0335] (34)3,5-Dichloro-4-(2-(N-phthalimido)ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 115.2° C.

[0336] (35)3,5-Dichloro-4-(3-(N-phthalimido)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 78.4° C.

[0337] (36)3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(20.5) 1.5377

[0338] (37)3,5-Dichloro-4-(3-(3-chloro-5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(22.5) 1.5429

[0339] (38)3,5-Dichloro-4-(3-(N-(1,2-dihydroxy-3-bromo-5-trifluoromethyl-2-oxo)pyridyl)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 119.5° C.

[0340] (39)3,5-Dichloro-4-(3-(2-benzimidazolylthio)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 120.7° C.

[0341] (40)3,5-Dichloro-4-(3-(2-benzothiazolylthio)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(22.5) 1.6322

[0342] (41)3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridyloxy)ethoxy)-1-(3,3-di-chloro-2-propenyloxy)benzenem.p. 67.0° C.

[0343] (42)3,5-Dichloro-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-di-chloro-2-propenyloxy)benzenen_(D) ^(21.3) 1.5359

[0344] (43) 3,5-Dichloro-4-(5-(5-trifluoromethyl-2-pyridyloxy)pentyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene n_(D)^(21.3) 1.5307

[0345] (44)3,5-Dichloro-4(6-(5-trifluoromethyl-2-pyridyloxy)hexyloxy)-1-(3,3-di-chloro-2-propenyloxy)benzenen_(D) ²1.3 1.5302

[0346] (45)3-Chloro-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(23.6) 1.5294

[0347] (46)3-Chloro-5-methyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(23.0) 1.5275

[0348] (47)3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(23.0) 1.5188

[0349] (48)3-Ethyl-5-methyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(23.0) 1.5170

[0350] (49)3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(25.0) 1.5525

[0351] (50)3,5-Diethyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzenen_(D) ^(20.0) 1.5192

[0352] (51)3,5-Diethyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-di-chloro-2-propenyloxy)benzene

[0353] (52)3,5-Dichloro-4-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0354] (53)3,5-Dichloro-4-(3-(3-bromo-5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0355] (54)3,5-Dichloro-4-(4-(3-bromo-5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0356] (55)3,5-Dichloro-4-(3-(3-fluoro-5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0357] (56)3,5-Dichloro-4-(4-(3-fluoro-5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0358] (57) 3,5-Dichloro-4-(3-(3,5-bistrifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0359] (58)3,5-Dichloro-4-(4-(3,5-bistrifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0360] (59) 3,5-Dibromo-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0361] (60)3,5-Dibromo-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)-1-(3,3-di-chloro-2-propenyloxy)benzene

[0362] (61)3,5-Dichloro-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0363] (62)3,5-Diethyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0364] (63)3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0365] (64)3-Chloro-5-methyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0366] (65)3,5-Diethyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0367] (66)3-Ethyl-5-methyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0368] (67)3-Chloro-5-methyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0369] (68)3,5-Dichloro-4-(2-(2-((2-(4-chlorophenyl)-1,3-dioxanyl)))ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0370] (69)3,5-Dichloro-4-(2-(2-((2-(4-trifluoromethylphenyl)-1,3-dioxanyl)))-ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0371] (70)3,5-Dichloro-4-(2-(2-((2-(4-trifluoromethoxyphenyl)-1,3-dioxanyl)))-ethoxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0372] (71)3,5-Dichloro-4-(3-(2-pyridyloxy)propylamino)-1-(3,3-dichloro-2-propenyloxy)benzenem.p. 76.2° C.

[0373] The following are production examples for the intermediatecompounds of the general formula [II] or [III].

INTERMEDIATE PRODUCTION EXAMPLE 1

[0374] A reaction vessel was charged with 5.0 g of 4-(benzyloxy)phenoland 100 ml of carbon tetrachloride, to which a solution 5.43 g oft-butyl hypochlorite dissolved in 5 ml of carbon tetrachloride wasslowly added dropwise, while stirring under ice cooling. After 24 hours,the reaction mixture was poured into water, followed by phaseseparation. The organic layer (i.e., carbon tetrachloride layer) waswashed with water, dried with anhydrous magnesium sulfate, andconcentrated to obtain a crude product. The crude product was subjectedto silica gel chromatography, which afforded 4.24 g of2,4-dichloro-4-(benzyloxy)phenol (63% yield).

[0375] A reaction vessel was charged with 5.10 g of 1,3-dibromopropane,2.40 g of potassium carbonate and 50 ml of N,N-dimethylformamide, towhich a solution of 4.24 g of 2,6-dichloro-4-(benzyloxy)phenol dissolvedin 10 ml of N,N-dimethylformamide was slowly added dropwise. Afterstirring at room temperature for 24 hours, the reaction mixture waspoured into water, and extracted twice with 150 ml of diethyl ether. Thecombined ether layer was washed with water, dried with anhydrousmagnesium sulfate, and concentrated to obtain a crude product. The crudeproduct was subjected to silica gel chromatography, which afforded 4.24g of 3,5-dichloro-4-(3-bromopropyloxy)-1-(benzyloxy)benzene (68% yield).

[0376] A reaction vessel was charged with 4.24 g of3,5-dichloro-4-(3-bromopropyl-oxy)-1-(benzyloxy)benzene, 1.33 g ofbenzoic acid, 1.65 g of potassium carbonate and 20 ml ofN,N-dimethylformamide. After stirring at room temperature for 24 hours,the reaction mixture was poured into water, and extracted twice with 150ml of diethyl ether. The combined ether layer was washed with water,dried with anhydrous magnesium sulfate, and concentrated to obtain acrude product. The crude product was subjected to silica gelchromatography, which afforded 3.75 g of3,5-dichloro-4-(3-benzoyloxy-propyloxy)-1-(benzoyloxy)benzene (80%yield).

[0377] A reaction vessel was charged with 3.75 g of3,5-dichloro-4-(3-benzoyl-oxypropyloxy)-1-(benzyloxy)benzene, 5.0 g of10% aqueous potassium hydroxide solution and 50 ml of methanol. Afterstirring at room temperature for 24 hours, the reaction mixture wasconcentrated. The concentrate was poured into water, and extracted twicewith 150 m of diethyl ether. The combined ether layer was washed withwater, dried with anhydrous magnesium sulfate, and concentrated toobtain a crude product. The crude product was subjected to silica gelchromatography, which afforded 2.56 g of3-(2,6-dichloro-4-(benzyloxy)phenoxy)-1-propyl alcohol (90% yield).

[0378] A mixture of 0.5 g of3-(2,6-dichloro-4-(benzyloxy)phenoxy)-1-propyl alcohol thus obtained,0.1 g of an oily mixture containing 60% sodium hydride, and 3 ml ofN,N-dimethylformamide was stirred at room temperature for 1 hour. Then,0.3 g of 2-chloro-5-trifluoromethylpyridine was added to this mixture,followed by heating to 100° C. After stirring continued for 1 hour, themixture was poured into 50 m of ice-water, and extracted with toluene ata total volume of 50 ml. The combined toluene layer was successivelywashed with diluted hydrochloric acid and aqueous sodium bicarbonatesolution, dried with magnesium sulfate, and concentrated. The residuewas silica gel chromatography, which afforded 0.5 g of1-benzyloxy-3,5-dichloro-4-[3-(5-trifluoro-methylpyridin-2-yloxy)propyloxy]benzene(67% yield).

[0379]¹H-NMR δ (ppm) [CDCl₃, TMS] 8.44 (1H, br, s), 7.76 (1H, dd),7.2-7.5 (5H), 6.90 (2H, s), 6.81 (1H, d), 5.00 (2H, s), 4.62 (2H, t),4.11 (2H, t), 2.31 (2H, quint.).

[0380] A reaction vessel was charged with 0.5 g of1-benzyloxy-3,5-dichloro-4-(3-(5-trifluoromethylpyridin-2-yloxy)propyloxy)benzeneand 50 ml of ethyl acetate, and the air in the vessel was replaced withnitrogen. Then, 0.3 g of 10% palladium carbon was added, and thenitrogen in the vessel was replaced with hydrogen, followed by stirringat room temperature for 24 hours. The hydrogen in the vessel wasreplaced with nitrogen, after which the reaction mixture was filteredthrough Celite, and the filtrate was concentrated, which afforded 0.36 gof 3,5-dichloro-4-(3-(5-trifluoromethylpyridin-2-yloxy)-propyloxy)phenol(92% yield).

[0381]¹H-NMR δ (ppm) [CDCl₃, TMS] 8.45 (1H, br, s), 7.75 (1H, dd), 6.77(2H, s), 6.75 (1H, d), 4.60 (2H, t), 4.15 (2H, t), 2.25 (2H, quint.)

[0382] The following are specific examples of the intermediate compoundof the general formula [II] or [III] under the corresponding compoundnumbers.

[0383] 1) 3,5-Dichloro4-(6-chloro-3-pyridylmethyloxy)phenol

[0384] 2) 3,5-Dichloro-4-(2,6-dichloro-3-pyridylmethyloxy)phenol

[0385] 3) 3,5-Dichloro-4-(2-(1-pyrazolynyl)ethoxy)phenol

[0386] 4) 3,5-Dichloro-4-(2-pyridylmethyloxy)phenol

[0387] 5) 3,5-Dichloro-4-(2-thienylmethyloxy)phenol

[0388] 6) 3,5-Dichloro-4-(2-furanylmethyloxy)phenol

[0389] 7) 3,5-Dichloro-4-(3-pyridylmethyloxy)phenol

[0390] 8) 3,5-Dichloro-4-(4-pyridylmethyloxy)phenol

[0391] 9) 3,5-Dichloro-4-(2-(2-thienyl)ethoxy)phenol

[0392] 10) 3,5-Dichloro-4-(2-(3-methylthiazol-2-yl)ethoxyphenol

[0393] 11) 3,5-Dichloro-4-(2,4,5-trichloroimidazolynylmethyloxy)phenol

[0394] 12) 3,5-Dichloro-4-(3,5-dimethyl-4-yloxazolynylmethyloxy)phenol

[0395] 13) 3,5-Dichloro-4-(2-(3-thienyl)ethoxy)phenol

[0396] 14) 3,5-Dichloro-4-(3-(4-pyridyl)propyloxy)phenol

[0397] 15) 3,5-Dichloro-4-((2-(1,4-benzodioxanyl))methoxy)phenol

[0398] 16) 3,5-Dichloro-4-((2-(5-formyl)furanyl)methoxy)phenol

[0399] 17) 3,5-Dichloro-4-((3-(6-methylpyridyl))methoxy)phenol

[0400] 18) 3,5-Dichloro-4-(2-(4-pyridylthio)ethoxy)phenol

[0401] 19) 3,5-Dichloro-4-(3-(3-pyridyl)propyloxy)phenol

[0402] 20) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl nicotinate

[0403] 21) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl isonicotinate

[0404] 22) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl quinolinate

[0405] 23) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl 2-furanate

[0406] 24) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl 2-thiophenate

[0407] 25) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl 3-thiophenate

[0408] 26) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl picolinate

[0409] 27) 3-(2,6-Dichloro-4-hydroxyphenoxy)propyl quinolinate

[0410] 28)3,5-Dichloro-4-(2-(2-((2-(4-chlorophenyl)-1,3-dioxanyl)))ethoxy)phenol

[0411] 29) 3,5-Dichloro-4-(3-(2-pyridylthio)propyloxy)phenol

[0412] 30) 3,5-Dichloro-4-(2-(6-ethoxy-2-benzothiazolyl)ethoxy)phenol

[0413] 31) 3,5-Dichloro-4-(2-(2-benzoxazolyl)ethoxy)phenol

[0414] 32)3,5-Dichloro-4-(2-methyl-2-(2-(6-chloro)pyridyloxy)propyloxy)phenol.

[0415] 33) 3,5-Dichloro-4-(2-(N-phthalimido)ethoxy)phenol

[0416] 34) 3,5-Dichloro-4-(3-(N-phthalimido)propyloxy)phenol

[0417] 35)3,5-Dichloro-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

[0418] 36) 3,5-Dichloro-4-(3-(3-chloro-5-trifluoromethyl-2-pyridyloxy)propyl-oxy)phenol

[0419] 37)3,5-Dichloro-4-(3-(N-(1,2-dihydroxy-3-bromo-5-trifluoromethyl-2-oxo)pyridyl)propyloxy))phenol

[0420] 38) 3,5-Dichloro-4-(3-(2-benzimidazolylthio)propyloxy)phenol

[0421] 39) 3,5-Dichloro-4-(3-(2-benzothiazolylthio)propyloxy)phenol

[0422] 40)3,5-Dichloro-4-(2-(5-trifluoromethyl-2-pyridyloxy)ethoxy)phenol

[0423] 41)3,5-Dichloro-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

[0424] 42)3,5-Dichloro-4-(5-(5-trifluoromethyl-2-pyridyloxy)pentyloxy)phenol

[0425] 43)3,5-Dichloro-4-(6-(5-trifluoromethyl-2-pyridyloxy)hexyloxy)phenol

[0426] 44)3-Chloro-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

[0427] 45)3-Chloro-5-methyl-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

[0428] 46) 3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

[0429] 47) 3-Ethyl-5-methyl1-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

[0430] 48) 3,5-Dichloro-4-(3-(5-tri flu oromethyl-2-pyridylamino)propyloxy)phenol

[0431] 49)3,5-Diethyl-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

[0432] 50)3,5-Diethyl4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

[0433] 51) 3,5-Dichloro-4-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

[0434] 52)3,5-Dichloro-4-(3-(3-bromo-5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

[0435] 53)3,5-Dichloro-4-(4-(3-bromo-5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

[0436] 54)3,5-Dichloro-4-(3-(3-fluoro-5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

[0437] 55)3,5-Dichloro-4-(4-(4-fluoro-5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

[0438] 56) 3,5-Dichloro-4-(3-(3,5bistrifluoromethyl-2-pyridyloxy)propyloxy)phenol

[0439] 57)3,5-Dichloro-4-(4-(3,5-bistrifluoromethyl-2-pyridyloxy)butyloxy)phenol

[0440] 58)3,5-Dibromo-4-(3-(5-trifluoromethyl-2-pyridyloxy)propyloxy)phenol

[0441] 59)3,5-Dibromo-4-(4-(5-trifluoromethyl-2-pyridyloxy)butyloxy)phenol

[0442] 60)3,5-Dichloro-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)phenol

[0443] 61)3,5-Diethyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)phenol

[0444] 62)3-Ethyl-5-methyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)phenol

[0445] 63) 3-Chloro-5-methyl-4-(3-(5-trifluoromethyl-2-pyridylamino)propyloxy)phenol

[0446] 64)3,5-Diethyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)phenol

[0447] 65)3-Ethyl-5-methyl-4-(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)phenol

[0448] 66)3-Chloro-5-methyl-4(4-(5-trifluoromethyl-2-pyridylamino)butyloxy)phenol

[0449] 67)3,5-Dichloro-4-(2-(2-((2-(4-chlorophenyl)-1,3-dioxanyl)))ethoxy)phenol

[0450] 68)3,5-Dichloro-4-(2-(2-((2-(4-trifluoromethylphenyl)-1,3-dioxanyl)))ethoxy)phenol

[0451] 69)3,5-Dichloro-4-(2-(2-((2-(4-trifluoromethoxyphenyl)-1,3-dioxanyl)))-ethoxy)phenol

[0452] The following are production examples for the intermediatecompounds of the general formula [VII].

REFERENCE PRODUCTION EXAMPLE 1

[0453] A reaction vessel was charged with 30.5 g of 4-hydroxyphenylbenzoate, 21.6 g of potassium carbonate, 20.8 g of1,1,3-trichloropropene and 100 ml of N,N-di-methylformamide. Afterstirring at room temperature for 15 hours, the reaction mixture waspoured into water, and extracted twice with 50 ml of diethyl ether. Thecombined ether layer was washed with water, dried with anhydrousmagnesium sulfate, and concentrated to obtain a crude product. The crudeproduct was subjected to silica gel chromatography, which afforded 44.1g of 4-(3,3-dichloro-2-propenyloxy)phenyl benzoate (96% yield).

[0454] A reaction vessel was charged with 44.1 g of4-(3,3-dichloro-2-propenyloxy)phenyl benzoate and 400 ml of methanol, towhich 33 g of 30% potassium hydroxide solution was slowly added dropwiseunder ice cooling. After stirring for 1 hour, the reaction mixture wasmade weakly acidic by the addition of 10% hydrochloric acid, andextracted twice with 150 ml of diethyl ether under salting out. Thecombined ether layer was washed with water, dried with anhydrousmagnesium sulfate, and concentrated to obtain a crude product. The crudeproduct was subjected to silica gel chromatography, which afforded 26.0g of 4-(3,3-dichloro-2-propenyloxy)phenol (87% yield).

[0455] A reaction vessel was charged with 26.0 g of4-(3,3-dichloro-2-propenyloxy)phenol and 500 ml of carbon tetrachloride,to which a solution of 27.1 g of tert-butyl hypochlorite dissolved in 20ml of carbon tetrachloride was slowly added dropwise, while stirringunder ice cooling. After 24 hours, the reaction mixture was poured intowater, followed by phase separation. The organic layer (i.e., carbontetrachloride layer) was washed with water, dried with anhydrousmagnesium sulfate, and concentrated to obtain a crude product. The crudeproduct was subjected to silica gel chromatography, which afforded 11.0g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol (32% yield),n_(D) ^(22.5) 1.5895.

REFERENCE PRODUCTION EXAMPLE 2

[0456] A solution of 50 g of 4-bromo-6-chloro-2-methylphenol and 42.5 gof benzyl bromide dissolved in 200 ml of N,N-dimethylformamide wasstirred at room temperature, to which 37.4 g of potassium carbonate wasadded, and the mixture was stirred for 12 hours. After completion of thereaction, the solvent was removed by distillation under reducedpressure, and the residue was added to 400 ml of diethyl ether, washedwith water, dried with anhydrous magnesium sulfate, and concentrated toobtain a crude product. The crude product was subjected to silica gelchromatography, which afforded 63 g of4-bromo-6-chloro-2-methyl-1-benzyloxybenzene (90% yield).

[0457] Then, 40 g of 4-bromo-6-chloro-2-methyl-1-benzyloxybenzene wasdissolved in 400 ml of tetrahydrofuran, followed by stirring at −70° C.,to which 76 ml of n-butyl lithium solution (in hexane, 1.69 mol/liter)was added dropwise, followed by further stirring at −70° C. for 2 hours.To this reaction mixture was added dropwise a solution of 13.3 g oftrimethoxyborane dissolved in 50 ml of tetrahydrofuran. Then, thereaction mixture was stirred for I hours, while warming to roomtemperature, and 100 ml of 10% aqueous hydrochloric acid solution wasadded in small portions, followed by stirring for 20 minutes. Thetetrahydrofuran layer was washed with water, dried with anhydrousmagnesium sulfate, and concentrated. The residue was mixed with 200 mlof toluene, and heated at 70° C. under stirring, to which 36 ml of 30%aqueous hydrogen peroxide solution was added dropwise. After heatingunder reflux for 1 hour, the reaction mixture was washed once withwater, twice with 10% ferrous sulfate and then ammonium water, and oncewith water, followed by phase separation. The toluene layer was driedwith anhydrous magnesium sulfate, and concentrated to obtain a crudeproduct. The crude product was subjected to silica gel chromatography,which afforded 29 g of 4-benzyloxy-3-chloro-5-methylphenol (91% yield).

[0458] To a solution of 27.3 g of 4-benzyloxy-3-chloro-5-methylphenoldissolved in 250 ml of chloroform and being stirred at 0° C. were added15.4 g of benzoyl chloride and then 13.3 g of triethylamine. Afterstirring at room temperature for 2 hours, the chloroform layer waswashed with water, dried with anhydrous magnesium sulfate, andconcentrated. The residue was subjected to silica gel chromatography,which afforded 35 g of 4-benzyloxy-3-chloro-5-methyl-1-benzoyloxybenzene(90% yield).

[0459] A reaction vessel was charged with 35 g of4-benzyloxy-3-chloro-5-methyl-1-benzoyloxybenzene and 200 ml of ethylacetate, and the air in the vessel was replaced with nitrogen. Then, 2 gof 10% palladium carbon was added, and the nitrogen in the vessel wasreplaced with hydrogen, followed by vigorous stirring at roomtemperature for 10 hours. The hydrogen in the vessel was replaced withnitrogen, after which the reaction mixture was filtered, and thefiltrate was concentrated. The residue was subjected to silica gelchromatography, which afforded 25 g of4-benzoyloxy-2-chloro-6-methylphenol (96% yield).

[0460] Then, 25 g of 4-benzoyloxy-2-chloro-6-methylphenol was dissolvedin 250 ml of chloroform, to which 12 g of chloromethyl methyl ether wasadded, while stirring at 0° C., and 21 g of N-ethyldiisopropylamine wasadded dropwise. After heating under reflux for 1 hour, the chloroformlayer was washed with water, and concentrated. The residue was subjectedto silica gel chromatography, which afforded 27.4 g of3-chloro-4-methoxymethoxy-5-methyl-1-benzoyloxybenzene (96% yield).

[0461] Then, 26 g of3-chloro-4-methoxymethoxy-5-methyl-1-benzoyloxybenzene was dissolved in200 ml of methanol, and the solution was stirred at room temperature for1 hour, while adding dropwise 60 ml of 10% aqueous potassium hydroxidesolution. After completion of the reaction, the solvent was removed bydistillation under reduced pressure. The residue was added to 150 ml ofwater, neutralized with 10% aqueous hydrochloric acid solution, andextracted with 200 ml of diethyl ether. The solvent was removed bydistillation under reduced pressure, and the residue was subjected tosilica gel chromatography, which afforded 17.4 g of3-chloro-4-methoxymethoxy-5-methylphenol (96% yield).

[0462] To a mixture of 10 g of 3-chloro-4-methoxymethoxy-5-methylphenol,7 g of potassium carbonate and 100 ml of N,N-dimethylformamide was addeddropwise a solution of 8 g of 1,1,3-trichloro-1-propene dissolved in 30ml of N,N-dimethylformamide, while stirring at room temperature. Afterstirring at room temperature for 12 hours, the reaction mixture waspoured into ice-water, and extracted twice with 200 ml of diethyl ether.The combined ether layer was washed with water, dried with anhydrousmagnesium sulfate, and concentrated. The residue was subjected to silicagel chromatography, which afforded 14.1 g of3-chloro-4-methoxymethoxy-5-methyl-1-(3,3-dichloro-2-propenyloxy)benzene(91% yield).

[0463] Then, 14.1 g of3-chloro4-methoxymethoxy-5-methyl-1-(3,3-dichloro-2-propenyloxy)benzenewas dissolved in 100 nm of 80% aqueous acetic acid solution, followed byheating under reflux with stirring for I hour. After completion of thereaction, the reaction mixture was mixed with 200 ml of water, andextracted twice with 200 ml of. diethyl ether. The combined ether layerwas washed with water, dried with anhydrous magnesium sulfate, andconcentrated. The residue was subjected to silica gel chromatography,which afforded 11.3 g of2-chloro-6-methyl-(3,3-dichloro-2-propenyloxy)phenol (93% yield), m.p.70.0° C.

[0464] The following is a production example for the intermediatecompounds of general formula [XIII].

REFERENCE PRODUCTION EXAMPLE 3 Production of3,5-dichloro4-(3-bromopropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene

[0465] A reaction vessel was charged with 10.6 g of 1,3-dibromopropane,5.53 g of potassium carbonate and 100 ml of N,N-dimethylformamide, towhich a solution of 30.5 g of2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol dissolved in 40 ml ofN,N-dimethylformamide was slowly added dropwise. After stirring at roomtemperature for 24 hours, the reaction mixture was poured into water,and extracted twice with 150 ml of diethyl ether. The combined etherlayer was washed with water, dried with anhydrous magnesium sulfate, andconcentrated to obtain a crude product. The crude product was subjectedto silica gel chromatography, which afforded 11.1 g of3,5-dichloro-4-(3-bromopropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene(77% yield), n_(D) ^(24.0) 1.5693.

[0466] The following are formulation examples in which “parts” are byweight and the present compounds are designated by the correspondingcompound numbers as described above.

FORMULATION EXAMPLE 1

[0467] Emulsifiable Concentrates

[0468] Ten parts of each of the present compounds (1) to (70) aredissolved in 35 parts of xylene and 35 parts of N,N-dimethylformamide,to which 14 parts of polyoxyethylene styrylphenyl ether and 6 parts ofcalcium dodecylbenzenesulfonate are added, and the mixture is wellstirred to give a 10% emulsifiable concentrate of each compound.

FORMULATION EXAMPLE 2

[0469] Wettable Powders

[0470] Twenty parts of each of the present compounds (1) to (70) areadded to a mixture of 4 parts of sodium lauryl sulfate, 2 parts ofcalcium lignin sulfonate, 20 parts of synthetic hydrated silicon oxidefine powder and 54 parts of diatomaceous earth, and the mixture isstirred with a mixer to give a 20% wettable powder of each compound.

FORMULATION EXAMPLE 3

[0471] Granules

[0472] Five parts of each of the present compounds (1) to (70), 5 partsof synthetic hydrated silicon oxide fine powder, 5 parts of sodiumdodecylbenzenesulfonate, 30 parts of bentonite and 55 parts of clay aremixed, and the mixture is well stirred. Then, a suitable amount of wateris added to the mixture, which is further stirred, granulated with agranulator and then air-dried to give a 5% granule of each compound.

FORMULATION EXAMPLE 4

[0473] Dusts

[0474] One part of each of the present compounds (1) to (70) isdissolved in a suitable amount of acetone, to which 5 parts of synthetichydrated silicon oxide fine powder, 0.3 part of PAP and 93.7 parts ofclay are added, and the mixture is stirred with a mixer. The removal ofacetone by evaporation gives a 1% dust of each compound.

FORMULATION EXAMPLE 5

[0475] Flowables

[0476] Twenty parts of each of the present compounds (1) to (70) aremixed with 1.5 parts of sorbitan trioleate and 28.5 parts of an aqueoussolution containing 2 parts of polyvinyl alcohol, and the mixture ispulverized into fine particles having a particle size of not more than 3μm with a sand grinder, to which 40 parts of an aqueous solutioncontaining 0.05 part of xanthan gum and 0.1 part of aluminum magnesiumsilicate are added and then 10 parts of propylene glycol are added. Themixture is stirred to give a 20% water-based suspension of eachcompound.

FORMULATION EXAMPLE 6

[0477] Oil Solutions

[0478] First, 0.1 part of each of the present compounds (1) to (70) isdissolved in 5 parts of xylene and 5 parts of trichloroethane. Then, thesolution was mixed with 89.9 parts of deodorized kerosine to give a 0.1%oil solution of each compound.

FORMULATION EXAMPLE 7

[0479] Oil-Based Aerosols

[0480] First, 0.1 part of each of the present compounds (1) to (70), 0.2part of tetramethrin, 0.1 part of d-phenothrin, and 10 parts oftrichloroethane are dissolved in 59.6 parts of deodorized kerosine, andthe solution is put in an aerozol vessel. Then, the vessel is equippedwith a valve, through which 30 parts of a propellant (liquefiedpetroleum gas) are charged under increased pressure to give an oil-basedaerosol of each compound.

FORMULATION EXAMPLE 8

[0481] Water-Based Aerosols

[0482] An aerosol vessel is filled with 50 parts of pure water and amixture of 0.2 part of each of the present compounds (1) to (70), 0.2part of d-allethrin, 0.2 part of d-phenothrin, 5 parts of xylene, 3.4parts of deodorized kerosine and 1 part of an emulsifier [ATMOS 300(registered trade name by Atlas Chemical Co.)]. Then, the vessel isequipped with a valve, through which 40 parts of a propellant (liquefiedpetroleum gas) are charged under pressure to give a water-based aerosolof each compound.

FORMULATION EXAMPLE 9

[0483] Mosquito-Coils

[0484] First, 0.3 g of each of the present compounds (1) to (70) ismixed with 0.3 g of d-allethrin, and the mixture is dissolved in 20 mlof acetone. The solution is uniformly mixed with 99.4 g of a carrier formosquito-coils (prepared by mixing Tabu powder, pyrethrum marc powderand wood flour in the ratio of 4:3:3) under stirring. The mixture iswell kneaded with 120 ml of water, molded and dried to give amosquito-coil of each compound.

FORMULATION EXAMPLE 10

[0485] Electric Mosquito-Mats

[0486] First, 0.4 g of each of the present compounds (1) to (70), 0.4parts of d-allethrin and 0.4 g of pipenyl butoxide are dissolved inacetone to have a total volume of 10 ml. Then, 0.5 ml of the solution isuniformly absorbed in a substrate for electric mosquito-mats having asize of 2.5 cm×1.5 cm×0.3 cm (prepared by forming a fibrillated mixtureof cotton linter and pulp into a sheet) to give an electric mosquito-matof each compound.

FORMULATION EXAMPLE 11

[0487] Heating Smoke Formulations

[0488] First, 100 mg of each of the present compounds (1) to (70) isdissolved in a suitable amount of acetone. Then, the solution isabsorbed in a porous ceramic plate having a size of 4.0 cm×4.0 cm×1.2 cmto give a heating smoke formulation of each compound.

FORMULATION EXAMPLE 12

[0489] Poison Baits

[0490] First, 10 mg of each of the present compounds (1) to (70) isdissolved in 0.5 ml of acetone, and the solution is uniformly mixed with5 g of solid bait powder for animals (Breeding Solid Feed Powder CE-2,trade name by Japan Clea Co., Ltd.). Then, the removal of acetone by airdrying gives a 0.5% poison bait of each compound.

[0491] The following test examples demonstrate that the presentcompounds are useful as an active ingredient of insecticidal/acaricidalagents. In these test examples, the present compounds are designated bythe corresponding compound numbers as described above and the compoundsused for comparison are designated by the corresponding compound symbolsas shown in Table 47. TABLE 47 Compound Chemical structure Remarks (A)

Compound disclosed in JP-A 48-86835/1973, page 23 (B)

Compound disclosed in JP-A 49-1526/1974, page 22

TEST EXAMPLE 1

[0492] Insecticidal Test Against Spodoptera litura

[0493] A 200-fold dilution containing an active ingredient at 500 ppm,which had been prepared by diluting with water an emulsifiableconcentrate of the test compound obtained according to FormulationExample 1, was absorbed at a volume of 2 ml in 13 g of an artificialdiet for Spodoptera litura, which had been prepared in a polyethylenecup having a diameter of 11 cm. Ten fourth-instar larvae of Spodopteralitura were set free in the cup. After 6 days, the survival of larvaewas examined to determine the mortality. The test was conducted induplicate.

[0494] As a result, it was found that the present compounds (1), (2),(5)-(7), (9)-(11), (14), (16)-(18), (20)-(26), (28)-(37) and (39)-(50)exhibited the m 80% or more. In contrast, both compounds (A) and (B) forcomparison exhibited the mortality of 0%.

TEST EXAMPLE 2

[0495] Test Against Tetranychus urticae Koch

[0496] Ten female adults of Tetranychus urticae Koch per one leaf wereallowed to parasitize to a potting bean at the primary leaf stageharvested for 7 days after seeding, and these pots were placed in athermostated room at 25° C. After 6 days, a chemical solution containingan active ingredient at 500 ppm, which had been prepared by dilutingwith water an emulsifiable concentrate of the test compound obtainedaccording to Formulation Example 1, was sprayed at a volume of 15 mlover each pot on a turntable. At the same time, 2 ml of the samesolution was drenched in the soil. After 8 days, the degree of damage onthe respective plants caused by Tetranychus urticae Koch was examined.The effects were determined according to the following criteria:

[0497] −: Damage is scarcely observed.

[0498] +: Damage is slightly observed.

[0499] ++: Damage is observed at the same level as in the non-treatedfield.

[0500] As a result, it was found that the present compounds (1), (7),(10), (15), (30), (32) and (33) were evaluated as “−” or “+”. In thecontrast, both compounds A and B for comparison were evaluated as “++”.

TEST EXAMPLE 3

[0501] Insecticidal Test Against Heliothis virescens

[0502] A dilution containing an active ingredient at 100 ppm, which hadbeen prepared by diluting with water an emulsifiable concentrate of thetest compound obtained according to Formulation Example 1, wasincorporated at a volume of 0.2 ml in an artificial diet. Asecond-instar larva of H. virescens was given the diet and bred in aplastic vessel. Ten insects were used by each treatment. After 6 days,the mortality was determined.

[0503] As a result, it was found that the present compounds (36), (42)and (43) exhibited the mortality of 80% or more. In contrast, bothcompounds (A) and (B) for comparison exhibited the mortality of 0%.

TEST EXAMPLE 4

[0504] Insecticidal Test Against Plutelle xylostella

[0505] A chemical solution containing an active ingredient at 50 ppm,which had been prepared by diluting an emulsifiable concentrate of thetest compound obtained according to Formulation Example 1 with watercontaining spreading agent RINOU (Nihon Nouyaku K.K.) to a degree suchthat the spreading agent had been 1000-fold diluted, was sprayed at avolume 25 ml over each pot of a potting cabbage at the five leaf stage.The treated plants were air dried, on which ten third-instar larvae ofPlutella xylostella were set free. After 4 days, the mortality wasdetermined.

[0506] As a result, it was found that the present compounds (36), (37),(42) and (45)-(48) exhibited the mortality of 80% or more. In contrast,both compounds (A) and (B) for comparison exhibited the mortality of 0%.

[0507] Industrial Applicability

[0508] The present compounds have excellent insecticidal/acaricidalactivity, so that they are satisfactorily effective for the control ofnoxious insects, mites and ticks.

1. A dihalopropene compound of the general formula:

wherein Z is oxygen, sulfur or NR⁴ and wherein R⁴ is hydrogen or C₁-C₃alkyl; Y is oxygen, sulfur or NH; X's are independently chlorine orbromine; R², R³ and R¹⁰ are independently halogen, C₁-C₃ haloalkyl orC₁-C₃ alkyl; t is an integer of 0 to 2; and R¹ is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆or Q₇ of the general formula:

wherein A is an optionally substituted 5-membered heterocyclic ringgroup containing 2, 3 or 4 nitrogen atoms and 1 or 2 carbon atoms; B isoxygen, S(O)_(q), NR⁹, C(═G¹)G² or G¹C(═G²); q is an integer of 0 to 2;R⁹ is hydrogen, acetyl or C₁-C₃ alkyl; G¹ and G² are independentlyoxygen or sulfur; R⁵, R⁶, R⁷, R¹¹ and R¹² are independently hydrogen,C₁-C₃ alkyl or trifluoromethyl; R¹³ and R¹⁴ are independently hydrogen,C₁-C₃ alkyl, trifluoromethyl or halogen; p is an integer of 0 to 6; ands is an integer of 1 to
 6. 2. The dihalopropene compound according toclaim 1, wherein A is a 5-membered heterocyclic ring group selected fromtriazolyl, tetrazolyl or thiadiazolyl and optionally substituted with(R⁸)_(r), wherein R⁸ is halogen, nitro, cyano, C₁-C₄ alkyl, C₁-C₃haloalkyl, C₁-C₄ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃haloalkylthio, C₁-C₂ alkylsulfinyl, C₁-C₂ alkylsulfonyl, C₁-C₂haloalkylsulfinyl, C₁-C₂ haloalkylsulfonyl, C₂-C₄ alkenyl, C₂-C₄haloalkenyl, C₂-C₄ alkynyl, C₂-C₄ haloalkynyl, amino, dimethylamino,acetamido, acetyl, haloacetyl, formyl, carboxyl, methoxycarbonyl, C₃-C₆cycloalkyl, (C₁-C₂ alkyl)aminocarbonyl or [di(C₁-C₂alkyl)amino]carbonyl, or R⁸ is phenyl, benzyl, phenoxy, benzyloxy orpyridyloxy, each of which is optionally substituted with halogen, C₁-C₄alkyl, C₁-C₃ haloalkyl, C₁-C₄ alkoxy or C₁-C₃ haloalkoxy; and r is aninteger of 0 to
 7. 3. The dihalopropene compound according to claim 1,wherein R² and R³ are independently halogen or C₁-C₃ alkyl; and t is 0.4. The dihalopropene compound according to claim 1, wherein R² and R³are independently chlorine, bromine, methyl, ethyl or isopropyl; and tis
 0. 5. The dihalopropene compound according to claim 1, wherein R² andR³ are both chlorine; and t is
 0. 6. The dihalopropene compoundaccording to claim 1, wherein R² is chlorine; R³ is methyl; and t is 0.7. The dihalopropene compound according to claim 1, wherein R² is ethyl;R³ is methyl; and t is
 0. 8. The dihalopropene compound according toclaim 1, wherein R² and R³ are both bromine; and t is
 0. 9. Thedihalopropene compound according to claim 1, wherein R² and R³ are bothethyl; and t is
 0. 10. The dihalopropene compound according to claim 1,wherein R² and R³ are independently halogen or C₁-C₃ alkyl; t is 1 or 2;and R¹⁰ is halogen or C₁-C₃ alkyl.
 11. The dihalopropene compoundaccording to claim 1, wherein R² and R³ are independently halogen orC₁-C₃ alkyl; t is 1 or 2; and R¹⁰ is halogen.
 12. The dihalopropenecompound according to claim 1, wherein Y and Z are both oxygen.
 13. Thedihalopropene compound according to claim 4, wherein Y and Z are bothoxygen.
 14. The dihalopropene compound according to claim 1, wherein R¹is Q₁.
 15. The dihalopropene compound according to claim 1, wherein R¹is Q₂.
 16. The dihalopropene compound according to claim 13, wherein R¹is Q₃.
 17. The dihalopropene compound according to claim 13, wherein R¹is Q₄.
 18. The dihalopropene compound according to claim 13, wherein R¹is Q₅.
 19. The dihalopropene compound according to claim 13, wherein R¹is Q₆.
 20. The dihalopropene compound according to claim 13, wherein R¹is Q₇.
 21. An insecticidal/acaricidal agent comprising the dihalopropenecompound according to claim 1 as an active ingredient.